Rican Patients Research Articles

Retinitis Pigmentosa Associated With EYS Gene Mutations in Puerto Rico: A Case Series.

Mutations in the EYS (eyes shut homolog) gene are a known cause of autosomal recessive retinitis pigmentosa (arRP). Pathogenic variants in EYS have been associated with a more severe clinical course compared to mutations in other retinitis pigmentosa (RP)-related genes. The prevalence of EYS-related arRP varies among different populations. To date, no studies have described the presence of EYS mutations in Puerto Rican patients. This case series aims to report and characterize EYS mutations in RP patients from Puerto Rico. This retrospective case series was conducted at two major ophthalmology clinics in Puerto Rico from 2019 to 2023. A chart review was performed to identify RPpatients who had mutations in the EYS gene, identified through the Invitae Inherited Retinal Disease Panel, which evaluates more than 300 genes. Collected data included demographic information (age and gender), ocular and medical history, clinical presentation of RP, best corrected visual acuity (BCVA), and genetic testing results. Seven Puerto Rican patients, three females (43%) and fourmales (57%), with a clinical diagnosis of RP, were found to have pathogenic EYS variants. Among them, four patients (57%) carried the c.5928-2A>G variant, two (29%) had c.6794del, one (14%) had c.1211dup, and one (14%) had c.3443+1G>T. Compound heterozygosity in the EYS gene was observed in two patients. Additionally, three variants of unknown significance (VUS) were identified. Patients exhibited a wide range of visual acuity; however, those older than 40 were found to be legally blind. Conclusions: This study provides evidence of EYS-related RP in Puerto Rican patients. Four truncating mutations in the EYS gene were identified, with c.5928-2A>G being the most frequent. Additionally, the novel EYS variant c.9263G>A (p.Gly3088Glu), classified as VUS, was identified in one patient.

A Descriptive Analysis of a Sample of Hispanic PCOS Patients Living in Puerto Rico [ID 2683511

INTRODUCTION: Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies during the reproductive years. Research has shown that Hispanic women with PCOS have the most severe phenotype, in terms of hyperandrogenism and metabolic disturbances. Absence of detailed characterization of PCOS in Puerto Rican patients poses significant barriers to translating research findings into clinical practice. Our aim is to provide an in-depth exploration of the gynecological profile of this population. METHODS: This was a cross-sectional study involving 105 female participants aged 21–45 years who underwent clinical evaluation during their routine health visit at endocrinology and gynecology clinics at the UPR-RCM clinics. The study cohort comprised 79 individuals with PCOS and 26 individuals without PCOS. IRB approval number is 2290034657 (B0790117). RESULTS: Significant differences were found in the prevalence of oligomenorrhea (90%; P<.001), amenorrhea (94.5%; P<.0004), clinical hirsutism (90.7%; P<.0001), and smoking (97.3%; P<.0001) among PCOS patients. These results align with existing literature on PCOS patients. There were no significant differences in menarche, thelarche, metrorrhagia, menorrhagia, sociodemographic profile, or toxic habits between the two groups. Additionally, both groups exhibited similarly high body mass index, fasting blood sugar, and hemoglobin A1C levels. CONCLUSION: Our study population’s characteristics align with those reported in other studies. However, the observed metabolic disturbances in our control group may be attributed to unique factors prevalent within the Puerto Rican population. Although this research contributes valuable insights, it is essential to acknowledge the study’s limitations, particularly the relatively small sample size. Further investigation and broader sampling are warranted to substantiate and refine these initial findings.

Advancing Primary Ciliary Dyskinesia Diagnosis through High-Speed Video Microscopy Analysis.

Primary ciliary dyskinesia (PCD) is an inherited disorder that impairs motile cilia, essential for respiratory health, with a reported prevalence of 1 in 16,309 within Hispanic populations. Despite 70% of Puerto Rican patients having the RSPH4A [c.921+3_921+6del (intronic)] founder mutation, the characterization of the ciliary dysfunction remains unidentified due to the unavailability of advanced diagnostic modalities like High-Speed Video Microscopy Analysis (HSVA). Our study implemented HSVA for the first time on the island as a tool to better diagnose and characterize the RSPH4A [c.921+3_921+6del (intronic)] founder mutation in Puerto Rican patients. By applying HSVA, we analyzed the ciliary beat frequency (CBF) and pattern (CBP) in native Puerto Rican patients with PCD. Our results showed decreased CBF and a rotational CBP linked to the RSPH4A founder mutation in Puerto Ricans, presenting a novel diagnostic marker that could be implemented as an axillary test into the PCD diagnosis algorithm in Puerto Rico. The integration of HSVA technology in Puerto Rico substantially enhances the PCD evaluation and diagnosis framework, facilitating prompt detection and early intervention for improved disease management. This initiative, demonstrating the potential of HSVA as an adjunctive test within the PCD diagnostic algorithm, could serve as a blueprint for analogous developments throughout Latin America.

Abstract 4403: The crosstalk between the tumor microbiome and epigenomic changes in penile squamous cell carcinoma

Abstract Penile squamous cell carcinoma (PSCC) is approximately three times more prevalent in Puerto Rico when compared to other ethnic groups in the United States. Moreover, the mortality rate for PSCC among Puerto Rican men is significantly higher when compared to the US population. Infection with human papillomavirus (HPV) has been identified as a risk factor for an average of 48% of PSCC cases in Puerto Rico. The molecular etiology of HPV+ and HPV- PSCC remains poorly understood. To date, the role of the microbiota in the pathogenesis of PSCC is unknown, as there are no studies that characterize the microbiome in association with penile cancer. Furthermore, the role of DNA methylation, which is an epigenetic alteration that can be found in cancer cells that can lead to changes in gene expression and cellular function, is also unknown. Therefore, there is an urgent need to address this knowledge gap. This study aims to analyze the DNA methylation patterns and bacterial communities in HPV-positive and HPV-negative PSCC tissues from Puerto Rican men. DNA was extracted from twenty-one fresh PSCC tissue samples from Puerto Rican patients. HPV status and genotyping were determined using the DNA ELISA kit HPV SPF10 protocol. DNA methylation assay was performed using the Infinium Methylation EPIC v2.0 BeadChip Kit to identify and compare average DNA methylation levels (%) in 7 HPV-positive and 14 HPV-negative penile cancer samples. Microbiota analyses were performed using 16S rRNA genes with the Illumina MiSeq platform. Demultiplexed data was deposited in QIITA for quality control and bioinformatic analyses and downstream analyses were done in R and Qiime2. Our results demonstrated that 45 loci methylation patterns were significantly different between HPV-positive and HPV-negative samples, with an adjusted p-value <0.1 (Benjamini-Hochberg method). Three loci methylation patterns were significantly affected by species diversity and richness. The abundance of Firmicutes, Proteobacteria, Bacteroidetes, Fusobacteria, and Actinobacteria was individually associated with number of affected loci (27, 19, 12, 6, and 3, respectively). We found that HPV status is associated with methylation patterns and microbiome in PSCC in Puerto Rican men. Both changes may be involved in triggering inflammatory responses and oncogenesis. Although many challenges must be overcome to dissect the specific interactions of coinfecting bacteria and methylation patterns during the penile cancer infectious process, our findings demonstrate that microbes may be involved in these cellular processes. Citation Format: Jorge Viera-Vera, Yarelis M. Roque-Reyes, Daniel Santiago-Negron, María Sánchez-Vázquez, Yakshi Ortiz Maldonado, Gabriel Borges-Vélez, Jasmine Figueroa-Díaz, Carlos A. Rivera-López, Niki M. Zacharias Millward, María J. Marcos-Martínez, Filipa Godoy-Vitorino, Antonio Puras-Baez, Julie Dutil, Josué Pérez-Santiago, Magaly Martínez-Ferrer. The crosstalk between the tumor microbiome and epigenomic changes in penile squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4403.

Abstract A007: Expression and activity of Rac, Cdc42, and their downstream effector PAK in Puerto Rican pancreatic cancer patients

Abstract Pancreatic ductal adenocarcinoma (PDAC) is often diagnosed after the localized tumor has metastasized, which decreases its survival rate to a grim 3%. Mortality from PDAC is also increasing in Puerto Rico with lower survival rates than in the US. Therefore, it is pivotal to identify viable targets for the late stages of PDAC. The small GTPase Ras is the most mutated oncogene in PDAC. Oncogenic Ras, as well as multiple oncogenic cell surface receptors, activate the related GTPases Rac and Cdc42, which in turn activate p21-activated kinase (PAK) by autophosphorylation (p-PAK), to drive cancer cell invasion, and thus metastasis. Rac and Cdc42 are overexpressed in 21% of PDAC patients and contribute to poor prognosis. To determine the feasibility of treating PDAC with Rac/Cdc42 inhibitors that we are developing, this study aims to identify the p-PAK levels and Rac/Cdc42 expression in PDAC tissue from Puerto Rican patients. The hypothesis is that p-PAK levels, as well as Rac/Cdc42 expression, are selectively elevated in high-grade invasive PDAC. Immunohistochemistry for p-PAK and immunofluorescence for Rac/Cdc42 were conducted in fixed, paraffin-embedded PDAC biopsy samples of Puerto Rican patients. Preliminary results demonstrate that higher p-PAK levels are correlated with stage 3 and stage 4 tissue, and Rac and Cdc42 are expressed in ductal regions of PDAC tissue. Taken together, p-PAK has potential as a diagnostic biomarker for high-grade PDAC and will aid patient stratification in the planned clinical trials for our lead Rac/Cdc42 inhibitor, MBQ-167. Citation Format: Anamaris Torres-Sanchez, Jahdiel Berrios-Rodriguez, Jerry Cruz-Rodriguez, Jasmin Contreras-Santini, Victor Carlo, Suranganie Dharmawardhane. Expression and activity of Rac, Cdc42, and their downstream effector PAK in Puerto Rican pancreatic cancer patients [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr A007.

Abstract A107: The role of social network and provider support on access to care in Puerto Rican and US Virgin Islands gynecologic cancer patients post-Hurricanes Maria and Irma

Abstract Background: Hurricanes Irma and Maria touched down on Puerto Rico (PR) and the US Virgin Islands in 2017 with devastating impacts. Essential infrastructure, services, and the overall environment were impacted, forcing residents to adapt or migrate amid these natural disasters. With Gynecologic cancers representing over 15% of all cancer in Puerto Rican women, these patients were at a high risk of experiencing challenges and barriers detrimental to their health outcomes. This study assessed how social networks (i.e., immediate family, friends, and neighbors) and provider (i.e., oncologists, oncology associations, and hospitals) support played a role in accessing health services by gynecologic cancer patients in the aftermath of the hurricanes. Methods: In-depth interviews were conducted to assess hurricane-related stressors and disaster responses. PR (n=24) and US Virgin Island (n=2) gynecologic cancer patients participated across 4 focus groups (December 2018-April 2019). Key cancer stakeholders were individually interviewed, consisting of oncology care providers and administrators (n=23) providing services in PR. All interviews were recorded, transcribed (verbatim), and coded with emerging themes using inductive methods. Results: The analysis highlighted the impact of stressors and multi-level responses on health outcomes for the patients. The identified emerging themes and subcodes included: 1) Health Access; 2) Stressors; 3) Emergency Response to Communication methods. Participants highlighted how their health needs were satisfied or not during the aftermath of the disasters primarily based on the availability of support from their social network and on recorded responses of available providers and clinics. They also detailed the expression of diverse stressors (i.e., primary, secondary, psychosocial, environmental) experienced while searching for health services. Regarding communications, patients and providers detailed several mechanisms of non-traditional patient-provider communication, such as WhatsApp group messaging, telephone robocalls for texting, leaving written notes at clinics or homes, and traveling outside PR to communicate with outside and local resources. Conclusion: The study demonstrated that social and provider support was critical in patients accessing care. A supportive social network facilitated access to health management, treatments, and primary service (i.e., water and electricity). Conversely, patients with minimal to no social support expressed difficulty improving these areas. Health providers also played an essential role with their patients and in the community by providing innovative alternative resources beyond planned emergency response. Implications for safety data management and sharing are in place when managing adverse outcomes in emergency planning. These results are imperative to include in future emergency preparedness plans for PR to prevent and mitigate the effects of natural disasters among vulnerable populations, such as cancer patients. Citation Format: Celeste M. Charchalac-Zapeta, Edna Acosta-Perez, Sandra I Garcia-Camacho, Mirza Rivera, Ana Patricia Ortiz Martinez. The role of social network and provider support on access to care in Puerto Rican and US Virgin Islands gynecologic cancer patients post-Hurricanes Maria and Irma [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr A107.

Abstract C058: Differential DNA methylation in HPV+ and HPV- penile tumors from Puerto Rican men

Abstract The incidence of penile squamous cell carcinoma (PSCC) in Puerto Rico is nearly three times higher when compared with other racial and ethnic groups in the United States. Mortality rate for PSCC is also significantly higher among Puerto Rican men when compared to the US population. Human papillomavirus (HPV) is a common virus, and its infection may increase the risk of developing PeCa. Despite the high incidence, the molecular mechanism of PSCC remains poorly understood. Our laboratory found that the prevalence of HPV in PSCC in Puerto Rican men is 49%. Due to the high rates of HPV infection and increased incidence of penile cancer in Puerto Rican men, there is a need to understand the pathogenesis of penile cancer. DNA Methylation is an epigenetic alteration that can be found in cancer cells, which can lead to changes in gene expression and cellular function. This study aims to analyze the DNA methylation patterns in HPV-positive and HPV-negative PSCC tissues from Puerto Rican men. DNA was extracted from twenty-four fresh PSCC tissue samples from Puerto Rican patients. HPV status and genotyping were determined using the DNA ELISA kit HPV SPF10 protocol. DNA was amplified and hybridized using PCR. We perform a DNA methylation assay using the Infinium Methylation EPIC v2.0 BeadChip Kit to identify and compare average DNA methylation levels (%) in the 9 HPV-positive and 15 HPV-negative penile cancer samples. Our results demonstrated 43 loci significantly different between HPV-positive and HPV-negative samples, with an adjusted p-value <0.1 (Benjamini-Hochberg method). Most of the hypermethylated loci were present in HPV-negative tumor samples. Additionally, we identified four methylated-differentially expressed genes: ANXA4, CACNA1C-AS1, UBXN2A, and DUOX1, which are found as uncharacterized proteins (open reading frames, ORFs) of the human genome with adjusted p-value <0.05. Studies have revealed that specific DNA methylation patterns could be linked with cancer development and progression. Identification of differentially methylated regions in HPV positive (HPV+) PSCC compared with HPV negative (HPV-) cases will provide much needed data to aid studies on early detection, prognosis, and development of therapeutic agents to reduce the morbidity and mortality from PeCa. Identification of differentially expressed genes and pathways in HPV positive (HPV+) PeCa compared with HPV negative (HPV-) cases will provide much needed data to aid studies on prevention, early detection, prognosis, and development of therapeutic agents to reduce the morbidity and mortality from PeCa. Citation Format: Yarelis M. Roque Reyes, María Sánchez-Vázquez, Josué Perez, Luis R. Llanos, Ingrid Montes, Jasmine Figueroa-Díaz, Carlos Rivera-Lopez, María Marcos, Antonio Puras, Magaly Martínez-Ferrer. Differential DNA methylation in HPV+ and HPV- penile tumors from Puerto Rican men [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr C058.

Differences in Outcomes by Place of Origin among Hispanic Patients with Kidney Failure.

Hispanic patients are known to have a higher risk of kidney failure and lower rates of home dialysis use and kidney transplantation than non-Hispanic White patients. However, it is unknown whether these outcomes differ within the Hispanic community, which is heterogeneous in its members' places of origins. Using United States Renal Data System data, the authors found similar adjusted rates of home dialysis use for patients originating from places outside the United States and US-born Hispanic patients, whereas the adjusted risk of mortality and likelihood of transplantation differed depending on place (country or territory) of origin. Understanding the heterogeneity in kidney disease outcomes and treatment within the Hispanic community is crucial in designing interventions and implementation strategies to ensure that Hispanic individuals with kidney failure have equitable access to care. Compared with non-Hispanic White groups, Hispanic individuals have a higher risk of kidney failure yet lower rates of living donor transplantation and home dialysis. However, how home dialysis, mortality, and transplantation vary within the Hispanic community depending on patients' place of origin is unclear. We identified adult Hispanic patients from the United States Renal Data System who initiated dialysis in 2009-2017. Primary exposure was country or territory of origin (the United States, Mexico, US-Puerto Rico, and other countries). We used logistic regression to estimate differences in odds of initiating home dialysis and competing risk models to estimate subdistribution hazard ratios (SHR) of mortality and kidney transplantation. Of 137,039 patients, 44.4% were US-born, 30.9% were from Mexico, 12.9% were from US-Puerto Rico, and 11.8% were from other countries. Home dialysis rates were higher among US-born patients, but not significantly different after adjusting for demographic, medical, socioeconomic, and facility-level factors. Adjusted mortality risk was higher for individuals from US-Puerto Rico (SHR, 1.04; 95% confidence interval [CI], 1.01 to 1.08) and lower for Mexico (SHR, 0.80; 95% CI, 0.78 to 0.81) and other countries (SHR, 0.83; 95% CI, 0.81 to 0.86) compared with US-born patients. The adjusted rate of transplantation for Mexican or US-Puerto Rican patients was similar to that of US-born patients but higher for those from other countries (SHR, 1.22; 95% CI, 1.15 to 1.30). Hispanic people from different places of origin have similar adjusted rates of home dialysis but different adjusted rates of mortality and kidney transplantation. Further research is needed to understand the mechanisms underlying these observed differences in outcomes.

MicroRNA-92b targets tumor suppressor gene FBXW7 in glioblastoma.

Glioblastoma (GBM) is a highly aggressive and lethal primary brain tumor. Despite limited treatment options, the overall survival of GBM patients has shown minimal improvement over the past two decades. Factors such as delayed cancer diagnosis, tumor heterogeneity, cancer stem cell survival, infiltrative nature of GBM cells, metabolic reprogramming, and development of therapy resistance contribute to treatment failure. To address these challenges, multitargeted therapies are urgently needed for improved GBM treatment outcomes. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression. Dysregulated miRNAs have been identified in GBM, playing roles in tumor initiation, progression, and maintenance. Among these miRNAs, miR-92b (miRNA-92b-3p) has been found to be overexpressed in various cancers, including GBM. However, the specific target genes of miR-92b and its therapeutic potential in GBM remain poorly explored. Samples encompassed T98G, U87, and A172 human GBM cell lines, GBM tumors from Puerto Rican patients, and murine tumors. In-situ hybridization (ISH) assessed miR-92b expression in patient tumors. Transient and stable transfections modified miR-92b levels in GBM cell lines. Real-time PCR gauged gene expressions. Caspase 3 and Trypan Blue assays evaluated apoptosis and viability. Bioinformatics tools (TargetScanHuman 8.0, miRDB, Diana tools, miRWalk) predicted targets. Luciferase assays and Western Blots validated miRNA-target interactions. A subcutaneous GBM Xenograft mouse model received intraperitoneal NC-OMIs or miR92b-OMIs encapsulated in liposomes, three-times per week for two weeks. Analysis utilized GraphPad Prism 8; statistical significance was assessed using 2-tailed, unpaired Student's t-test and two-way ANOVA as required. This study investigated the expression of miR-92b in GBM tumors compared to normal brain tissue samples, revealing a significant upregulation. Inhibition of miR-92b using oligonucleotide microRNA inhibitors (OMIs) suppressed GBM cell growth, migration, and induced apoptosis, while ectopic expression of miR-92b yielded opposite effects. Systemic administration of liposomal-miR92b-OMIs in GBM xenograft mice resulted in reductions in tumor volume and weight. Subsequent experiments identified F-Box and WD Repeat Domain Containing 7 (FBXW7) as a direct target gene of miR-92b in GBM cells. FBXW7 acts as a tumor suppressor gene in various cancer types, and analysis of patient data demonstrated that GBM patients with higher FBXW7 mRNA levels had significantly better overall survival compared to those with lower levels. Taken together, our findings suggest that the dysregulated expression of miR-92b in GBM contributes to tumor progression by targeting FBXW7. These results highlight the potential of miR-92b as a therapeutic target for GBM. Further exploration and development of miR-92b-targeted therapies may offer a novel approach to improve treatment outcomes in GBM patients.

323 Perceived Stress and Access to Care in Parents of Children Living a Diagnostic Odyssey in Puerto Rico

OBJECTIVES/GOALS: Diagnostic odyssey is the time it can take to a patient for receiving a diagnosis. Diagnostic process in rare diseases can be complex due to the heterogeneity of symptoms and lack of access to care. We aim to evaluate the association between diagnostic odyssey, perceived stress, and access to care, in parents of Puerto Rican patients with a rare disease. METHODS/STUDY POPULATION: We propose a cross-sectional study in parents of 100 children who received an uninformative whole exome sequencing (WES) report during a scheduled appointment with their geneticist. Discussion of WES results during clinical session, followed by a Perceived Stress Scale (PSS-10) and semi-structured interview to explore the experience of access to care during the diagnostic process will be arranged. Observation and interviews will be recorded. Data analysis and descriptive statistics will be calculated using STATA. Statistical associations (OR) will be estimated using generalized linear models at a 5% significance level. RESULTS/ANTICIPATED RESULTS: We expect to find high perceived stress in parents of Puerto Rican pediatric individuals having rare diseases, especially among single mothers. We will be able to identify limited access to care in Puerto Rico, especially in the testing pre-authorization process and long waits for geneticist appointments. Demand for advanced diagnostics is above the number of medical geneticists available in Puerto Rico, which triggers delayed diagnosis, management, and counseling. Therefore, these could affect the health disparities in our population with rare diseases. DISCUSSION/SIGNIFICANCE: This descriptive study will evaluate perceived stress in parents of pediatric patients living a diagnostic odyssey in Puerto Rico. No study has described perceived stress and access to care in this Hispanic population with undiagnosed conditions. Findings will contribute to a deep understanding of diagnostic process and limited access to care.

Abstract P1-06-07: Interrogating the Molecular Profile of Breast Cancer Tumors in Hispanics Living in Puerto Rico (PRH)

Abstract Breast cancer (BC) has the highest incidence and mortality rates among Puerto Rican women. However, the representation of Hispanics living in Puerto Rico (PRH) in breast cancer clinical trials may be limited due to the lack of a defined genetic profile from BC tumors in Puerto Rican patients. Mutations in genes associated with tumor suppressors, tumor progression, and genome stability are shared among all BCs. Nonetheless, differences in the frequency of these mutations have been observed among racial/ethnic groups. This study aims to characterize the genomic landscape of BC tumors in PRH and identify the most common genetic mutations. We conducted secondary data analysis to evaluate the mutational profile of 189 BC tumors from PRH who underwent NGS testing from 2015 to 2020 and compared the prevalence of breast tumor somatic mutations and gene amplifications with profiles reported for other races/ethnicities available through The Cancer Genome Atlas (TCGA) and the AACR Genomics Evidence Neoplasia Information Exchange (GENIE). The most mutated genes among PRH breast tumors were TP53, PIK3CA, ARID1A, NF1, and RB1, while the most frequent gene amplifications were FGF19, H3F3B, ZN703, MCL1, and ADGRA2. H1047R and E545K were the most frequent specific mutations in PRH for PIK3CA; R248Q and R273C for TP53 and Q1212*, S634* and Q557fs for ARID1A. Statistically significant differences were found between populations. This study reports a unique mutational profile of BC tumors in PRH and makes comparisons with non-Hispanic and USH populations, providing novel knowledge to increase Hispanic representation in future BC studies and treatments. Citation Format: Norianne Martinez-Viota, Xavier Bittman-Soto, Ingrid M. Montes-Rodriguez, Kelvin Carrasquillo, Hilmaris Centeno-Girona, Marcia Cruz-Correa. Interrogating the Molecular Profile of Breast Cancer Tumors in Hispanics Living in Puerto Rico (PRH) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-06-07.

The RAS-24: Development and validation of an adherence-to-medication scale for severe mental illness patients

Several studies have found that most patients with severe mental illness (SMI) and comorbid (physical) conditions are partially or wholly nonadherent to their medication regimens. Nonadherence to treatment is a serious concern, affecting the successful management of patients with SMIs. Psychiatric disorders tend to worsen and persist in nonadherent patients, worsening their overall health. The study described herein aimed to develop and validate a scale (the Ralat Adherence Scale) to measure nonadherence behaviors in a culturally sensitive way. Guided by a previous study that explored the primary reasons for nonadherence in Puerto Rican patients, we developed a pool of 147 items linked to the concept of adherence. Nine experts reviewed the meaning, content, clarity, and relevance of the individual items, and a content validity ratio was calculated for each one. Forty items remained in the scale's first version. This version was administered to 160 patients (21-60 years old). All the participants had a diagnosis of bipolar disorder, major depressive disorder, or schizoaffective disorder. The STROBE checklist was used as the reporting guideline. The scale had very good internal consistency (Cronbach's alpha = 0.812). After a factor analysis, the scale was reduced to 24 items; the new scale had a Cronbach's alpha of 0.900. This adherence scale is a self-administered instrument with very good psychometric properties; it has yielded important information about nonadherence behaviors. The scale can help health professionals and researchers to assess patient adherence or nonadherence to a medication regimen.

Diagnosing Alzheimer Disease: Which Dementia Screening Tool to Use in Elderly Puerto Ricans with Mild Cognitive Impairment and Early Alzheimer Disease?

AbstractBackgroundMost of the time, Alzheimer Disease (AD)’s diagnosis is not made at its earliest periods and prodromal stages, for instance at Mild Cognitive Impairment (MCI) and Early Alzheimer Disease (E‐AD) stage. Commonly, AD’s diagnosis is made when significant impairment interferes with the habitual daily activities (1). Our pilot study, serves to demonstrate a correlation between the screening tools, including the Mini‐mental Status Exam (MMSE), Montreal Cognitive Assessment (MoCA) and Clinical Dementia Rating Scale (CDR), and the biological biomarkers in the cerebral spinal fluid (CSF) (Amyloid Beta 1‐42 (Aβ42 pg/mL), Tau proteins (tTau (pg/mL) and tTau/Aβ42 ratio in Puerto Ricans > 55 years old with MCI and E‐AD. To our knowledge, this is the first study trying to create a correlation between memory tests scores and underlying AD pathology to improve early detection in elderly Puerto Ricans.MethodThirty participants were evaluated including, demographics, clinical characteristics, memory scales and CSF biomarkers. CSF biomarkers (Aβ42, tTau protein, and tTau/Aβ42 ratio) were determined using the Meso Scale Discovery Platform (MSD). Associations between memory scales (MOCA, MMSE, CDR) and CSF markers were performed using Spearman’s rho correlation.ResultOur study revealed statistical association in favor of a direct relationship between MMSE and tTau/Aβ42 ratio in CSF (p= .022, 95.00% CI = [‐.69, ‐.07] (Figure 1). We found a trend towards significance with an inverse relationship with MMSE and Aβ42 (p=.069) (Figure 2) and a direct relationship with MMSE and tTau (p= .098) (Figure 3). Besides, MoCA and tTau/Aβ42 ratio had a statistically significant direct relationship (p = 0.035) (Figure 4). There was no significant statistical association between CDR test with CSF biomarkers in elderly Puerto Ricans.ConclusionMMSE was the dementia screening test consistently identifying a statistically significant or a‐trend‐towards a significant association with the CSF Alzheimer Disease’ s biomarkers (Aβ42, tTau protein, and tTau/Aβ42 ratio) in elderly Puerto Ricans with MCI and E‐AD. Clinically, > 55 y/o Puerto Rican patients with MCI and E‐AD should be screened with MMSE for a higher likelihood of earlier detection and, thus, initiation of disease‐modifying treatment.

Clinical, immunological and genetic characterization of patients with X‐linked agammaglobulinemia in Costa Rica

AbstractX‐linked agammaglobulinemia is caused by mutations in the gene encoding Bruton tyrosine kinase. It produces an arrest in the maturation and differentiation of B cells with very low levels of all immunoglobulins isotypes. The aim of the study was to characterize the clinical, immunological and genetic defects in patients with XLA in Costa Rica. Sixteen cases were identified over a period of 30 years, a case every 2 years, approximately. Three patients were asymptomatic and diagnosis was made on family history. The average age of onset of symptoms was 1.46 years‐old (0.08–6.1). Six patients (44%) had onset of symptoms before 1 year of age and 12 (81%) patients before 5 years of age. The average age of diagnosis was 3.63 years‐old (0.17–13, SD 3.51 years‐old the average time between the onset of symptoms and the diagnosis was 2.5 years (2.5 months to 12 years, SD 3 years). The initial reason to study the patients was a recurrent infection, family history of XLA, arthritis and neutropenia. Four patients had pneumonia and two had suppurative lung disease. Nine patients had recurrent infections: acute otitis media, sinusitis, mastoiditis and recurrent diarrhoea. Three patients presented with arthritis. Neutropenia as an isolated event was not identified in any case. All patients receive monthly IVIG and no deaths were reported. Three new likely pathogenic/pathogenic variants in BTK gene have been described in our population. This is the first report of XLA Costa Rican patients and their BTK mutations.

Colorectal cancer vaccines: in silico identification of tumor-specific antigens associated with frequent HLA-I alleles in the costa rican Central Valley population

Colorectal cancer is a complex disease in which uncontrolled growth of abnormal cells occurs in the large intestine (colon or rectum). The study of tumor-specific antigens (neoantigens), molecules that interact with the immune system, has been extensively explored as a possible therapy called in silico cancer vaccine. Cancer vaccine studies have been triggered by the current high-throughput DNA sequencing technologies. However, there is no universal bioinformatic protocol to study tumor-antigens with DNA sequencing data.
 We propose a bioinformatic protocol to detect tumor-specific antigens associated with single nucleotide variants (SNVs) or “mutations” in colorectal cancer and their interaction with frequent HLA alleles (complex that present antigens to immune cells) in the Costa Rican Central Valley population. We used public data of human exome (DNA regions that produce functional products, including proteins). A variant calling analysis was implemented to detect tumorspecific SNVs, in comparison to healthy tissue. We then predicted and analyzed the peptides (protein fragments, the tumor specific antigens) derived from these variants, in the context of its affinity with frequent alleles of HLA type I of the Costa Rican population.
 We found 28 non-silent SNVs, present in 26 genes. The protocol yielded 23 strong binders peptides derived from the SNVs for frequent alleles (greater than 8%) for the Costa Rican population at the HLA-A, B and C loci. It is concluded that the standardized protocol was able to identify neoantigens and this can be considered a first step for the eventual design of a colorectal cancer vaccine for Costa Rican patients. To our knowledge, this is the first study of an in silico cancer vaccine using DNA sequencing data in the context of the Costa Rican HLA alleles.

33475 Histologic characteristics of early mycosis fungoides in Puerto Rico

The histologic diagnosis of early mycosis fungoides (eMF) is one of the most difficult tasks in dermatopathology. Experts have attempted to define specific histopathologic criteria for the diagnosis of eMF, but a definite consensus has not been reached. We assessed the prevalence of a series of predetermined histologic parameters in Puerto Rican patients with a diagnosis of eMF. This was a retrospective study from 2015 to 2021 at the University of Puerto Rico. Only Puerto Rican patients with an unequivocal diagnosis of eMF (Stage 1A/1B) were included.

Dermatologic manifestations in patients with the Hermansky–Pudlak syndrome types 1 and 3

BackgroundThe Hermansky–Pudlak syndrome (HPS) is a genetically heterogeneous group of diseases characterized by oculocutaneous albinism, bleeding diathesis, and systemic complications. It is the most common genetic disorder in Puerto Rico. These patients are at a significant risk of developing a variety of skin complications and little is known about the prevalence of dermatologic diagnoses in this population.ObjectivesTo report dermatologic manifestations in patients with Hermansky–Pudlak syndrome (HPS). Secondary aims include skin concerns, sun protection habits, barriers to dermatologic care, and skin cancer knowledge.MethodsCross-sectional study with twenty-nine Puerto Rican patients who carried a clinical diagnosis of HPS type 1 or type 3 through a telephonic questionnaire.ResultsTwenty-nine patients participated with a mean (SD) age of 37.3 (16.8) years and the majority were female (69%). The most common diagnoses were skin cancer (34.5%), acne (34.5%), bacterial skin infections (34.5%), warts (24%), urticaria (17.2%), and psoriasis (17.2%). The most common skin concerns were dry skin (62.1%), hair loss (58.9%), redness (34.5%), moles (31%), and rash (31%). The most common sun protection behavior was wearing a shirt that covers the shoulders (93.1%, often or always) and the least common was wearing a hat (24.1%, often or always). Higher income was significantly associated with being more likely to use sunscreen often or always (OR = 3.38, 95% CI 1.02–11.18, p = 0.04). Those in northern urban areas were significantly less likely to report barriers to dermatologic care (OR = 0.13, 95% CI 0.02–0.76, p = 0.02).ConclusionsThis study provides an important overview of the most common self-reported skin manifestations in patients with HPS. Unfortunately, a high prevalence of cutaneous malignancy was reported. The results stress the need for adequate care and potential interventions to promote sun protection behaviors and skin cancer prevention.

Thrombolysis Experience in Costa Rica Compared Against Individual Patient Data from two Randomized Controlled Trials

ObjectivesWe sought to compare thrombolysis outcomes from the Costa Rican Stroke Registry Program (CRSRP) with published individual patient data from NINDS and CLOTBUST-ER trials using matching and outcome modeling from randomized clinical trials (RCTs). Materials and methodsA retrospective observational study matching subjects on baseline characteristics, from the CRSRP, the control arm of CLOTBUST-ER, and the interventional arm of NINDS trials. Day 7-10/discharge modified Rankin Score (mRS), and early mortality was compared between matched subjects. A mortality model derived from RCTs was developed, and outcomes were compared at similar baseline NIHSS scores. CRSRP symptomatic hemorrhage (SICH) rate was compared with an Ibero-American cohort (IAC). ResultsOf 540 CRSRP patients, 351 received rt-PA under 3 hours and were matched with NINDS subjects yielding 292 pairs; 161 CRSRP subjects treated within 4.5 hours were matched with CLOTBUST-ER subjects resulting in 151 pairs. The proportion of patients achieving excellent outcomes (mRS 0-1) did not differ between CRSRP and either NINDS or CLOTBUST-ER (CRSRP vs NINDS: 36.6% vs 32.9%, p=0.3; CRSRP vs CLOTBUST-ER: 26.5% vs 24.5%, p=0.8). Mortality was higher for CRSRP vs CLOTBUST-ER (7.3% vs 0.7%, p=0.006), but not vs NINDS (6.5% vs 4.5%, p=0.4). A pooled mortality model derived from 15 RCTs representing 4410 patients (R2=0.39) showed CRSRP and NINDS within expected mortality, while CLOTBUST-ER showed lower than expected mortality. CRSRP SICH rate equaled IAC (5.7% vs 5.7%; p=0.9). ConclusionsFunctional outcomes and SICH of thrombolysed Costa Rican patients compared favorably with published datasets, with a potential increase in early mortality.

Abstract 2462: Rac and p-PAK expression among Puerto Rican breast cancer patients

Abstract Breast cancer is the most common cancer among US women and is the second leading cause of death from cancer. Since metastasis is a major cause of death from breast cancer, we focused on Rac, a key metastasis driver regulating cancer cell migration and invasion. The direct downstream effector of Rac, p21-activated kinase (PAK), is auto-phosphorylated (in Thr 423) when activated by Rac to promote cancer metastasis. Accordingly, Rac and PAK expression is associated with higher stages and grades of multiple cancers and is also increased in breast ductal carcinoma and lymph node metastases. The breast cancer incidence in Puerto Rico (PR) is lower than that of the mainland US; however, mortality rates are higher due to increased invasion and metastasis. Therefore, the objective in this study was to determine Rac and phospho (p)-PAK expression in breast cancer tissues from Puerto Rican patients. Consecutive cases of formalin-fixed paraffin embedded infiltrating mammary carcinomas from core needle biopsy samples were obtained from the Auxilio Mutuo Hospital, San Juan, PR. Our initial study was limited to estrogen receptor (ER)/progesterone receptor (PR) positive (+) patients with variable human epidermal growth factor receptor (HER2) status. Of the 16 patients studied, 10 were HER2 negative and 6 were HER2 positive. Histologic tumor grade via Nottingham criteria was determined and immunohistochemical stains for ER, PR, HER2 protein and Ki-67 were performed, as well as HER2 in situ hybridization for final determination of HER2 status. To evaluate the expression of Rac1, we used immunofluorescence (IMFL) with specific antibodies. p-PAK status was evaluated via immunohistochemistry (IHC) with specific antibodies to p-Thr423-PAK. The IMFL and IHC scores were determined by analyzing the staining intensity graded as follows: 0, no staining; 1, weak staining; 2, moderate staining; 3, strong staining. There were no significant differences in Rac1 expression based on HER2, ER, or PR status or Tumor Grade. Since Rac1 is activated via upstream receptor signaling such as HER2, we determined p-PAK staining as a measure of Rac activity. p-PAK staining was detected in ductal carcinoma (DC) in situ and invasive DC, with stronger staining in cancer cells infiltrating the surrounding tissue. p-PAK levels were elevated in HER2 positive compared to HER2 negative breast tumor tissue, independent of ER or PR status. Based on this data, we posit that selective Rac activation in HER2 positive breast cancers contribute to enhanced cancer malignancy in Puerto Rican patients. This will be validated by a larger sample size of breast cancer tissue comparing HER2/ER/PR status and cancer grade from Puerto Rican (Hispanic) and Caucasian patients. Citation Format: Mariangeline I. Gonzalez Ortiz, Magaly Martinez-Ferrer, Victor P. Carlo, Suranganie Dharmawardhane. Rac and p-PAK expression among Puerto Rican breast cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2462.

Abstract 3675: Epigenetic variations associated with therapy resistance among prostate tumors from Puerto Rican men

Abstract Prostate cancer (PCa) is the leading cause of cancer-related death in Puerto Rican (PR) men, a population at higher risk of developing the disease than other Hispanic/Latino groups. But the relationship between this phenomenon and epigenetics, and how this relationship explains PCa racial and ethnic health disparities are controversial. The purpose of this study was to expand on the knowledge regarding epigenetic differences in terms of DNA methylation to enable risk stratification and treatment selection in this genetically admixed population. In addition, we aim to assess differential DNA methylation patterns associated with drug resistance in PCa in PR Hispanic/Latino men. Since epigenetic changes and modifications represent critical components of carcinogenesis and progression, we are expecting differential methylation levels between aggressive vs. indolent, and resistant vs. non-resistant cases. Prostate tumors from PR men were stratified based on Gleason score. Methylation levels were measured by Illumina Infinium Methylation EPIC BeadChip DNA methylation platform, and bioinformatic analyses. In parallel, DNA methylation profiles were also analyzed using genomic DNA from PCa cells selected for resistance to androgen depletion, enzalutamide resistance, or docetaxel resistance. We identified 1,225 differentially methylated genes in prostate tumors compared with normal adjacent tissues, and 141 differentially methylated genes between aggressive vs. indolent tumors. Additionally, 723 differentially methylated genes were found in therapy resistant cell lines compared to parental controls. Analysis of the methylated genes obtained from aggressive prostate tumors from Puerto Rican patients and therapy-resistant PCa cell lines revealed four overlapping methylated genes: RNF220, FAM65B, PRDM16, and DGKH. Further analysis of PCa cells resistant to androgen depletion, enzalutamide, or docetaxel demonstrated impaired cellular migration of resistant phenotypes upon DNA methyltransferase (DNMT) inhibition using 5-azacytidine or zebularine compared to parental cell lines. DNMT1 was associated with resistance in PCa cell lines, and future studies will include silencing of methyltransferases will evaluation of drug re-sensitization. These findings provide critical insight into the epigenetic landscape of aggressive prostate tumors among PR men and highlight several candidate methylation biomarkers for assessing risk in this population. Citation Format: Carlos J. Diaz Osterman, Anders Berglund, Shannalee Martinez, Camila Luis, Julie Dutil, Jaime Matta, Jarline Encarnacion-Medina, Carmen Ortiz-Sanchéz, Liang Wang, Jasreman Dhillon, Youngchul Kim, Hyun Y. Park, Gilbert Ruiz-Deya, Kosj Yamoah, Jong Y. Park. Epigenetic variations associated with therapy resistance among prostate tumors from Puerto Rican men [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3675.