Need For Genetic Counseling Research Articles

EP512: Identifying clinical and psychological factors associated with genomics-related outcomes in a centralized sequencing protocol

Given the discrepancy between genetic counseling need and availability, a continual question in the genetic counseling literature is identifying individuals who may most benefit from meeting with a genetic counselor. Additionally, it’s critical to elicit patient perspectives when evaluating the outcomes of genomics services. Here, we identify clinical and psychological factors associated with genomics-related outcomes in a population of adults with suspected inborn errors of immunity enrolled in a large sequencing protocol. Specifically, the genomics-related outcomes in question are primarily practical tasks of psychosocial illness management, including being able to explain the condition to people who may need to know, knowing who else in the family may be at risk, and planning for one’s own future and the future of their children; one items refers to emotional regulation. A Redcap survey assessing psychological and illness characteristics was emailed to adults enrolled on a genetic sequencing protocol in the National Institute of Allergy and Infectious Diseases Centralized Sequencing Program and who were also suspected to have an inborn error of immunity. Outcomes were assessed using the previously-validated genomic outcomes scale (GOS). Psychosocial data was measured using the Patient-Reported Outcomes Measurement Information System (PROMIS) profile scale. Data was analyzed in R statistical software using descriptive statistics, correlations, and multiple regression models. We analyzed 314 responses from a pool of 1038 invited individuals (30.3% response rate). Respondents were 59% female and had a median age of 48. Approximately 45% of individuals reported having a genetic diagnosis, and 73% reported living with their diagnosis for over 10 years. The mean score for the GOS was 15.1 out of a total score of 25 (standard deviation = 4.4), in which higher scores corresponding to greater empowerment and adaptation to disease. Multiple linear regression found that individuals reporting having a genetic diagnosis for their condition, having higher functional ability, and having a family member with the same condition were significantly more likely to have higher GOS scores (ß = 0.2, p<0.001; ß = 0.15, p<0.01, and ß = 0.11, p<0.05, respectively). When examining individual items of the GOS, individuals reporting a genetic diagnoses were most significantly more likely to report feeling confident in planning for their or their children’s future (p<1.5x10-7 ) and explaining their illness (p<0.05). Among those with a genetic diagnosis, the specific diagnosis was not associated with GOS score. We found that individuals reporting having a genetic diagnosis and individuals reporting less functional disability were more likely to score higher on the GOS. Patients without a genetic diagnosis endorsed being able to explain their condition and feeling able to plan for their children's future to a lesser extent than those with a self-reported molecular diagnosis. These topics may merit special attention during counseling, particularly for those with a negative genomic evaluation. Further research is needed to determine how having a genetic diagnosis plays a role in psychosocial outcomes, as well as to elucidate the potential relationship between functional disability and psychosocial outcomes, and how sequencing programs can best assist these individuals.

Clinical, laboratory, and mutational profile of children with glucose phosphate isomerase deficiency: a single centre report.

Glucose phosphate isomerase (GPI) deficiency is an autosomal recessive condition with mutations in the GPI gene on chromosome 19q13.1. Patients present with congenital non-spherocytic hemolytic anemia, and occasionally intellectual disability. In this study, we describe the clinical, hematological and biochemical parameters in the largest single-center cohort consisting of 17 GPI-deficient cases. Demographic and clinical data were noted, and red cell enzyme activity levels were estimated. Mutation analysis was done by single-stranded-conformation polymorphism, restriction-fragment length polymorphism and Sanger's sequencing of exon 12 of the GPI gene. The male-to-female ratio was 0.7:1, median age at diagnosis was 5.0years, 82.3% of patients had severe neonatal jaundice, and 13.3% had subtle neurological manifestations. Median Hb and MCV levels were 6.3g/dl and 130.2fl. Splenectomized patients required fewer transfusions. Sixteen of 17 patients had the pathogenic c.1040G > A (p.Arg347His) homozygous mutation in exon12 of the GPI gene, and one had the pathogenic c.1414C > T(p.Arg472Cys) homozygous mutation in exon 16. In summary, we report that neonatal jaundice, macrocytosis and high prevalence of p.Arg347His variant were predominant in GPI deficiency with prominent lack of neurological manifestations, and we emphasize the benefits of splenectomy and the need for genetic counseling.

Retrospective Analysis of Clinicopathological Features and Familial Cancer History of Synchronous Bilateral Breast Cancer.

Bilateral breast cancer is a strong predictor of BRCA 1/2 mutation and hence one criterion indicated for hereditary genetic testing. The purpose of this study is to assess the characteristics of synchronous bilateral breast cancer (SBBC) and its association with personal and familial cancer traits. Patients diagnosed with SBBC in our institute between 1992 and 2018 were retrospectively reviewed, and the information of clinicopathological features, personal and family cancer history were analyzed. Of the 307 SBBCs enrolled, the growing case number generally aligned with the regional breast cancer incidence after the era of population-based mammography screening. SBBC patients had similar cancer stages but worse survival outcomes than those in the standard scenario. A total of 42.0% had mixed pathological diagnoses, and 22.8% had discordant immunohistochemistry (IHC) subtypes from both sides, which contributed to treatment challenges. The correlation of SBBC with hereditary breast and ovarian cancer (HBOC) syndrome was strongly implied, as 20.7% of our SBBC patients with known familial cancer histories had HOBC-related familial cancers (breast, ovarian, or prostate cancers). These findings highlight the need for genetic counseling and germline mutation testing in patients with SBBC. Early PARP inhibitor treatment should also be considered in high-risk cases for outcome improvement.

Prevalence and predictors of colour vision defects among Egyptian university students.

Nowadays, widespread usage of colours increases the need for accurate estimation of colour vision defects and their effect on performing daily activities and study/work tasks. To determine the prevalence and predictors of colour vision defects among Assiut university students and to identify their relationship with self-reported visual function and perceived difficulties in performing daily activities. A cross-sectional study was conducted among 1426 students at Assiut University, Egypt. Data were collected by self-administered questionnaire consisting of: personal characteristics, prior awareness of colour vision defects, difficulties in daily colour vision activities, and visual function. Colour vision was assessed using Ishihara's test of colour deficiency. The prevalence of colour vision defects among students was 6.9% (red-green colour vision was 4.3% and total colour blindness was 2.6%). Students with colour vision defects had significantly higher odds ratios for difficulties in daily activities and study/work tasks related to colour perception. Students with colour vision defects had significantly lower mean values of general health, role difficulties, and colour vision scores compared to students with normal colour insight. Male sex and family history of colour vision defects were risk factors. A non-negligible percentage of Egyptian university students had colour vision defects, which had a negative impact on performing daily activities, executing study/work tasks, and choice of study/work specialties. Colour vision defects affected quality of life with regard to general health, role difficulties and colour vision. Male sex and family history of colour vision defects are nonmodifiable risk factors. This emphasizes the need for genetic counselling, especially in consanguineous marriage.

Genetic and reproductive consequences of consanguineous marriage in Bangladesh.

IntroductionThis study aimed to assess the prevalence, sociodemographic factors, reproductive consequences, and heritable disease burdens associated with consanguineous marriage (CM) in Bangladesh.MethodsA total of 7,312 families, including 3,694 CM-families, were recruited from 102 locales of 58 districts of Bangladesh. Using a standard questionnaire, we collected medical history and background sociodemographic data of these families. Family history was assessed by pedigree analysis. Fertility, mortality, secondary sex ratio, selection intensity, lethal equivalents were measured using standard methods.ResultsThe mean prevalence of CM in our studied population was 6.64%. Gross fertility was higher among CM families, as compared to the non-CM families (p < 0.05). The rate of under-5 child (U5) mortality was significantly higher among CM families (16.6%) in comparison with the non-CM families (5.8%) (p < 0.01). We observed a persuasive rise of abortion/miscarriage and U5 mortality rates with the increasing level of inbreeding. The value of lethal equivalents per gamete found elevated for autosomal inheritances as compared to sex-linked inheritance. CM was associated with the incidence of several single-gene and multifactorial diseases, and congenital malformations, including bronchial asthma, hearing defect, heart diseases, sickle cell anemia (p < 0.05). The general attitude and perception toward CM were rather indifferent, and very few people were concerned about its genetic burden.ConclusionThis study highlights the harmful consequences of CM on reproductive behavior and the incidence of hereditary conditions. It essences the need for genetic counseling from premarital to postnatal levels in Bangladesh.

Pseudohypoparathyroidism in a child

Pseudohypoparathyroidism (Albright hereditary osteodystrophy) is a rare inherited disease of the skeletal system caused by impaired calcium and phosphorus metabolism that mimics hypoparathyroidism. It is often accompanied by mental and physical retardation. The disease is characterized by a pronounced clinical polymorphism, which is based on genetic heterogeneity. In the bone tissue there are changes typical of hyperparathyroidism: diffuse osteoporosis, the appearance of cysts (so-called brown tumors, giant cell tumors). Calcium, which is released from the bones, is deposited as calcifications in the subcutaneous tissue, as well as in the kidneys, muscles, myocardium, the walls of the large arteries, eye conjunctiva and periphery of the cornea. The cause of pseudohypoparathyroidism is a congenital defect — a genetically determined kidneys and skeleton resistance to parathyroid hormone. A diagnostic algorithm for monitoring of patients with pseudohypoparathyroidism is presented. In the presence of clinical symptoms that give reason to suspect pseudohypoparathyroidism, it is advisable to determine total and ionized calcium and phosphorus in the blood, urinary calcium excretion, as well as blood level of parathyroid hormone. Elevated blood parathyroid hormone and phosphorus along with low calcium in the blood and urine allow the diagnosis to be made. Timely diagnosis and clarification of the genesis of each syndrome are important for optimizing the treatment of these conditions and prevention of possible complications, as well as for determining the need for genetic counseling.

Knowledge and attitudes about genetic counseling in patients at a major hospital in Addis Ababa, Ethiopia.

Previous work at St. Paul's Hospital Millennium Medical College (SPHMMC) in Addis Ababa, Ethiopia, demonstrated a need for genetic counseling (GC) services, with 4% of pediatric, neonatal intensive care, and prenatal patients identified as having indications for genetic evaluation (Quinonez et al, 2019). The aim of this study was to investigate SPHMMC patients' familiarity with, knowledge of, and attitudes toward GC services. Surveys were adapted from previous work in North America populations (Riesgraf et al, 2015 and Gemmell et al, 2017) and administered to 102 patients, and results were compared to North American populations using Student's t test. 30% of respondents reported at least some familiarity with GC, primarily via the media or healthcare providers. Patients had generally positive attitudes toward GC, reporting they would trust information provided by a genetic counselor and that GC is in line with their values. Knowledge of GC showed similar trends overall when compared to results from North American populations. Our work indicates limited exposure to GC in this population, but generally positive feelings toward GC. Patients' attitudes toward GC were comparable to rural North American populations surveyed using the same tool on most items; however, cultural differences including views on abortions and directiveness of healthcare providers could account for discrepancies and are important considerations when implementing genetic services globally.

Intrafamilial communication of hereditary breast and ovarian cancer genetic information in Italian women: towards a personalised approach.

Genomic testing expansion is accompanied by an increasing need for genetic counselling and intrafamilial communication. Genetic counselling can play an important role in facilitating intrafamilial communication and relationships. We conducted a cross-sectional, multicenter study including 252 Italian women, using a questionnaire divided in two sections, the first one to be filled after the pre-test counselling and the second after receiving BRCA test results. We assessed the factors influencing intrafamilial disclosure of genetic information for hereditary breast and ovarian cancer, family members with whom probands are more prone to share genetic information, and the perceived understanding of information received by counselees during genetic counselling. Women were accompanied to the counselling more often by their husband/partner. Among those with a positive BRCA test result, 49% intended to communicate it to their offspring and 27% to their husband/partner. Younger women, those living with their husband/partner, and those who described family communication as open/profound and spontaneous/sincere had a higher probability of being accompanied during genetic counselling and discuss about it with relatives. Spontaneous/sincere or open/profound family communication and joyful/happy familial relationships were associated with the decision to undergo genetic testing as a responsibility towards relatives. Women had a good understanding of counselling contents (mean score 9.27 in a scale 1-10). Genetic counselling providers should consider that genetic information disclosure does not depend only on the clarity of the information provided, but also on pre-existing intrafamilial communication and relationships, family structure and marital status, indicating the need for a personalised approach accounting for these factors.

Intra-familial communication of hereditary breast and ovarian cancer information in Italian women

Abstract Background Genomic testing expansion for hereditary breast and ovarian cancer (HBOC) comes with an increased need for genetic counseling and intra-familial communication. Genetic counseling can play an important role in facilitating intra-familial communication and relationships, thus avoiding misunderstandings within the family. Methods We conducted a cross-sectional, multicenter study including 252 Italian women, using a questionnaire divided in two sections; the first to be filled after the pre-test counseling and the second after receiving the genetic test results. This aimed at assessing the factors influencing the disclosure of genetic information for HBOC, family members that probands share genetic information with, and the degree of understanding of the information received by the counselees during genetic counseling. Results Women were accompanied to the counseling more by their husbands/partners. Among those with a positive test result, 49% shared it with their offspring and 27 % with their husband/partner. Younger women, those living with their husbands/partners and those who described family communication as open/deep had a higher probability of being accompanied at the genetic counseling and discuss about it with relatives. Being alone at the genetic counseling was significantly associated to non-existing familial relationship (p = 0.003) and problematic intra-familial communication (p = 0.005). Sincere or joyful familial relations were associated with the decision to undergo genetic testing as a responsibility towards relatives. Women had a good understanding of the counseling (mean score 9.2 in a scale1-10). Discussion Genetic counseling providers should consider that the disclosure of genetic information does not depend only on the clarity of the information provided, but also on pre-existing intra-familial communication and relationship, family structure and marital status, indicating the need of a personalized approach based on these factors. Key messages The disclosure of genetic information from women to their relatives in the case of HBOC is a complex relational process, which poses practical and ethical problems for individuals and families. Genetic counseling providers should be able to advice their patients on the importance of genetic information disclosure, considering, also, the pre-existing intra-familial communication dynamics.

Adaptation and preliminary validation of the genetic counseling outcome scale (GCOS-24) in a Brazilian genetic counseling setting

Health professionals working in services providing genetic counseling need objective instruments to assess genetic counseling outcomes and also to “give a voice” to those using these services. Lack of knowledge regarding such outcomes may directly impact the effectiveness and the potential benefits of counseling, quality of life, health promotion, and empowerment of those receiving counseling. There are very few instruments available for most countries, however there are none in Brazil. In this context, this study aimed to adapt and preliminarily validate the Genetic Counseling Outcome Scale (GCOS-24), a Patient-Reported Outcome Measure (PROM), originally developed in British English. This methodological study recruited 278 individuals attending a medical genetic service at a Brazilian university hospital. We performed the translation, back-translation, semantic validation, pilot study and field study for testing of some psychometric properties. The instrument's internal consistency and test-retest reliability (stability) were assessed using Cronbach's alpha coefficient and Intraclass Correlation Coefficient, respectively. The Brazilian version of the GCOS-24 presented face and content validity, satisfactory internal consistency (Cronbach's α = 0.71), and moderate stability (ICC = 0.52). It was considered reliable, easily understood and relevant to assessing the genetic counseling outcomes for the study participants. Its construct validity still needs to be assessed to verify the instrument's internal structure and its potential use to measure change in empowerment following genetic counseling provided by Brazilian clinical genetics services.

Integrated molecular profiling of young and elderly patients with triple-negative breast cancer indicates different biological bases and clinical management strategies.

Age at the time of breast cancer diagnosis not only predicts clinical outcome but also indicates distinct molecular characteristics that provide the rationale for appropriate treatment strategies. However, to the authors' knowledge, little is known regarding the molecular profile and biological basis of triple-negative breast cancers (TNBCs) occurring in young and elderly patients. Using the study institution's largest, single-center, multiomics TNBC data set, the authors analyzed the clinical and genomic features of young (aged ≤39years) and elderly (aged ≥65years) patients with TNBC. In the current study, a total of 50 patients, 354 patients, and 69 patients, respectively, were grouped as young, intermediate, and elderly patients with TNBC. Young patients with TNBC had worse short-term survival, upregulation of DNA repair, cell cycle and RNA metabolism gene sets, frequent pathogenic germline variants, and predominant homologous recombination deficiency-related mutational signatures. Several copy number alterations also were found to be enriched in young patients with TNBC. Nearly one-half of the TNBC cases in elderly patients were of the luminal androgen receptor subtype. TNBC in elderly patients was identified as being associated with severe fibrosis; a lower Ki-67 index; and somatic mutations in PIK3CA, KMT2D, ERBB2, ERBB3, and their corresponding pathways. Elderly patients with TNBC also were more likely to harbor targetable mutations. The findings of the current study indicated that young patients with TNBC had an enhanced cell cycle, which may have helped to explain their inferior short-term survival, whereas the homologous recombination deficiency and enriched pathogenic germline variants observed among young patients with TNBC suggested the need for genetic counseling and testing, as well as the potential use of DNA damage agents and poly(adenosine diphosphate ribose) polymerase (PARP) inhibitors. Molecular characteristics of elderly patients with TNBC, although suggesting less response to chemotherapy, provided a rationale for the routine detection of actionable somatic mutations.

Genetic testing for Alzheimer's disease: trends, challenges and ethical considerations.

Advances in personal genomics have made predictive genetic testing increasingly popular. The purpose of this review is to examine and summarize recent literature regarding the ethical concerns and considerations surrounding genetic testing for Alzheimer's disease. Four basic bioethical principles can be applied in the context of genetic testing: autonomy, nonmaleficence, beneficence and justice. The concepts of clinical validity, clinical utility and personal utility are also necessary for the ethical deliberation of genetic testing for Alzheimer's disease. Ethical considerations can differ among three distinct settings present in the literature: research, clinical and direct-to-consumer services. Studies have found that the negative psychosocial impact of genetic test results on the individual is limited, but emphasize the importance of pre/posttesting genetic counselling. The literature should ideally inform policy-making around genetic testing. There exists an urgent need for regulation, particularly in the direct-to-consumer (DTC) market, since interest for testing in this context is rapidly growing. Standardized protocols for disclosure should be developed, and there is a need to find ways to meet the growing need for genetic counselling. Importantly, comprehensive, evidence-based regulation requires that research be conducted in different contexts with more diverse participants.

Increasing the Clinical Psychiatric Knowledge Base About Pathogenic Copy Number Variation.

Specific copy number variants (CNVs) have been robustly associated with intellectual disability, autism, and schizophrenia. Most of the literature focus has been on documenting the existence of these phenomena. There are few data to guide therapeutic choices for these “orphan” diseases. We call for systematic and longitudinal case reports which, if carefully conducted, may provide crucial initial knowledge to guide therapeutics. We provide a step-by-step overview, a tailored set of consensus criteria for high-quality case reports, and a specific set of learning resources.

Development of a telegenetics program in the Asia-Pacific/Middle East region.

15 Background: BRCA mutations is emerging as an agnostic marker for PARPi. Accessibility to genetic counselling is limited due to shortage of manpower and access to institutions that provide it. Our aim was to look at the incidence of pathogenic germline mutations in India/UAE and develop a virtual pathway, aimed at increasing accessibility to genetic counselling. Methods: 864 patients(pts) were tested in the UAE and India for germline mutations. Based on discussion between physicians and patients, an urgent need for genetic counseling was identified. A virtual platform (telegenetics) was constructed for those who sought genetic counseling due to a personal or family history of malignancies. Referral of pts was either self-based or through a treating physician. Primary goals included 1) ease of access for pts, 2) increase comprehension of the indications, implications and consequences of genetic testing, 3) decrease physician time in the clinic. 10 questions were developed determine pt and physician satisfaction. Results: 241(28.9%)pts had a pathogenic variant in BRCA1/BRCA. 115pts were enrolled in the pilot phase of the tele genetics program; all physician referred. Counselling was by a dedicated trained genetic counsellor through voice-call(43.5%), video-conferencing(47.8%) or in person when requested (8.7%). All pts completed a satisfaction survey. Majority of pts were comfortable sharing information on a virtual platform(80%), were happy with the quality of virtual connection(85%), and felt comfortable connecting with the genetic counselor(90%). Information is currently being collected from referring physicians. Conclusions: Our ongoing pilot phase reveals improved pt satisfaction and understanding of the information provided. A mobile application has been developed to enhance pt accessibility/convenience and physician connectivity with the testing phase of the app currently on going. To our knowledge this is the first tele genetics program to target the middle east/Asia pac region that is targeted to cope with increase in pt volumes, expand appropriate referrals, starting with pts who have a personal or family history of cancers, expanding to more complex high risk diseases over time.

Genetic Counseling and Testing in a Community Setting: Quality, Access, and Efficiency.

There is an increasing need for genetic counseling and testing for individuals diagnosed with cancer, as treatment may be affected by the results. In addition, the identification of individuals before a diagnosis of cancer allows for optimal surveillance and early detection and prevention of cancer. With the recognition that as much as 10% of all cancers are hereditary, there is a growing need to improve access to genetic counseling and genetic testing, both before and at the time of diagnosis. This article focuses on models of identifying at-risk patients, including underserved communities; providing genetic counseling and testing in community practices; using telehealth; and collaborating with nongenetics health care providers and technological solutions to maximize efficiency and access.

Genetic counselling and testing of susceptibility genes for therapeutic decision-making in breast cancer—an European consensus statement and expert recommendations

An international panel of experts representing 17 European countries and Israel convened to discuss current needs and future developments in BRCA testing and counselling and to issue consensus recommendations. The experts agreed that, with the increasing availability of high-throughput testing platforms and the registration of poly-ADP-ribose-polymerase inhibitors, the need for genetic counselling and testing will rapidly increase in the near future. Consequently, the already existing shortage of genetic counsellors is expected to worsen and to compromise the quality of care particularly in individuals and families with suspected or proven hereditary breast or ovarian cancer. Increasing educational efforts within the breast cancer caregiver community may alleviate this limitation by enabling all involved specialities to perform genetic counselling. In the therapeutic setting, for patients with a clinical suspicion of genetic susceptibility and if the results may have an immediate impact on the therapeutic strategy, the majority voted that BRCA1/2 testing should be performed after histological diagnosis of breast cancer, regardless of oestrogen receptor and human epidermal growth factor receptor 2 (HER2) status. Experts also agreed that, in the predictive and therapeutic setting, genetic testing should be limited to individuals with a personal or family history suggestive of a BRCA1/2 pathogenic variant and should also include high-risk actionable genes beyond BRCA1/2. Of high-risk actionable genes, all pathological variants (i.e. class IV and V) should be reported; class III variants of unknown significance, should be reported provided that the current lack of clinical utility of the variant is expressly stated. Genetic counselling should always address the possibility that already tested individuals might be re-contacted in case new information on a particular variant results in a re-classification.

Determinants associated with making prenatal screening decisions in a national study

This study sought to evaluate the associations between background exposures and psychological determinants, among postpartum Jewish and Arab women, relative to actual prenatal test endorsement. The independent and aggregative effects of contextual features and the subjective opinions and attitudes relative to a prenatal testing were evaluated, using logistic regressions. After accounting for contextual features, Jews with positive vs. negative opinions on screening were significantly more likely to undergo a prenatal screening. Specifically, having more favourable ideas on pregnancy termination, among Jews, was associated with a greater likelihood of triple test, nuchal translucency and ultrasound uptake as compared with those that refused. Similarly, Arabs who were more inclined to abort the pregnancy had a greater chance of using nuchal translucency and ultrasound vs. those that declined testing. As the preferences for prenatal test outcomes are multifaceted and vary according to population group, a better understanding of the factors involved in making testing choices could help ease the decision-making process.Impact StatementWhat is already known on this subject? The choice to undergo prenatal screening tests is influenced by various determinants, which include: social, demographic and emotional factors that vary by cultural preferences. Indeed, women integrate (subjective) beliefs and values that extend beyond rational (objective) reasoning when estimating whether or not to undergo testing. It may then be that, prenatal test choices might be, influenced less by actual risk status and more so by emotional factors. And while, the latter are more likely to be amendable, and thus influence changes in perception, the effect of psychological exposures on the decision making process in the genetic testing context, especially among Israeli Jews and Arabs, has been understudied.What the results of this study add? The current study extends the focus by addressing the role of evaluative beliefs and emotional factors involved with formulating prenatal screening judgments relative to actual testing among individuals with diverse profiles (Israeli Jews and Arabs). What was clarified was that background factors and psychological perceptions, such as having supportive attitudes on screening and a willingness to undergo abortion were, for the most part, related to prenatal test uptake. Concomitantly, these involve dense decision-making practices that can be difficult to approximate, as cultural settings and individual preferences often have an impact on intention-to-test.What the implications are of these findings for clinical practice and/or further research? Culturally appropriate counselling that would account for personal preferences alongside actual risk appraisals could enable pregnant women to make informed and autonomous prenatal testing choices. The integration of socio-demographics, psychological correlates and other contextual factors into a theoretical framework, studied uniquely by sub-populations, could enrich future research. Such research can, in turn, provide a clearer picture of the social need for genetic counselling, help customise local interventions, and on a broader scale inform national policy.

Genetic counselors on the frontline of precision health.

By enabling precise genetic diagnosis and treatment there is great potential for inexpensive, accurate, and widely accessible genomic information to transform health care and improve the general well-being of virtually every person. To maximize this potential, approaches to genetic counseling and the role of genetic counselors will need to adapt to fit changing clinical and commercial needs worldwide. This will require overcoming multiple challenges including an inadequate workforce; development and implementation of alternate models of service delivery; integration of new technologies to improve, extend, and expand services; and support for equitable education and counseling among all populations. Genetic counselors are aptly poised to take on these challenges. The result will be better informed patients and families more capable of utilizing genetic information appropriately, making autonomous decisions about their care, and modifying their approach to disease risk to actively contribute to their health. The contributors to this issue of Seminars discuss how key areas of genetic counseling need to evolve and how genetic counselors can play a role in shaping the future of precision health.

Abstract P4-06-18: Clinical application of multigene panel testing and genetic counseling for hereditary/familial breast cancer risk assessment: Prospective single center study

Abstract Background The identification of individuals at elevated risk for hereditary cancers has allowed the development of consensus recommendations for cancer screening and prevention. The introduction of multigene panels may identify more individuals with breast cancer gene mutations than does testing for BRCA1/2 alone. Therefore, the multigenerational panel increase the need for genetic counseling suggesting preventive approach or cancer-specific screening to patients and family members. The rapid clinical introduction of multigene panel testing, however, have several issues such as low- to moderate-risk gene mutations and clinical recommendations. We collect the mutation results and clinical recommendations after testing with multigene panel and giving genetic counseling. Methods We had developed multigene panel consisted of 64 genes related to hereditary cancer through previous study and prospectively enrolled 104 individuals who were appropriate candidates for hereditary breast cancer evaluation. The patients were tested with 64-gene panel(Celemics) and results were provided by us 4˜10 weeks later. We checked the family history of cancer and made a pedigree before testing. Result Among 104 participants, 26 patients harbored deleterious mutations, most commonly in high to moderate-risk breast/ovarian cancer genes (BRCA1/2, BRIP, RAD51 and RAD51D), Lynch syndrome gene(MSH6) and other genes(FH, SPINK1). We recommended the cancer-specific screening and/or preventive approach for mutation-positive patients and suggested additional genetic test for the family members. Among them, 6 (23%) patients received Risk reducing procedures (Prophylactic mastectomy or oophorectomy) and most of them(19 patients(73%)) received cancer specific screening. Conclusion We demonstrate the use of multigene panel testing for hereditary breast cancer and will suggest the process of the genetic counseling including indication and results analysis with multigene panel testing. Citation Format: Lee E-S, Han W, Kim Y, Rhu J, Park JH, Kim K-E, Ju YW, Kim R, Lee H-B, Moon H-G, Noh D-Y. Clinical application of multigene panel testing and genetic counseling for hereditary/familial breast cancer risk assessment: Prospective single center study [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-06-18.

Contemporary Sarcoma Diagnosis, Genetics, and Genomics.

Sarcomas include diverse mesenchymal neoplasms with widely varied prognosis, clinical behavior, and treatment. Owing to their rarity and histologic overlap, accurate diagnosis of sarcomas can be challenging. Our approach has evolved dramatically in the past few decades, where novel insights into the molecular pathogenetic basis for sarcomas has dramatically (re)shaped contemporary diagnosis, building on a largely morphology- and clinical presentation-based strategy. Examples include the introduction of novel immunohistochemical markers that serve as surrogates for molecular genetic alterations and identification of characteristic molecular alterations. Accordingly, cytogenetic and molecular genetic analyses, such as conventional karyotyping, fluorescence in situ hybridization, reverse transcription-polymerase chain reaction, and targeted sequencing, have increasingly been incorporated into the routine diagnostic work-up of these neoplasms. For those sarcomas with complex cytogenetic changes that lack specific alterations, additional testing is often directed toward identifying lines of differentiation and excluding pathognomonic (cyto-)genetic alterations. Although some gene rearrangements are diagnostic of particular sarcoma types, certain fusion partners, most notably EWSR1, are not tumor specific (and may, in fact, also be found in benign tumors). Correlation with clinical, radiologic, morphologic, and immunohistochemical findings is particularly important in tumors with such rearrangements to establish the correct diagnosis, acknowledging the inherent limitations of diagnostic tests. The recognition of sarcomas occurring in cancer predisposition syndromes is critical, with implications not only for the index patient but also potentially for family members, including the need for genetic counseling and sometimes particular types of surveillance. Together, contemporary sarcoma evaluation involves combining the initial morphologic evaluation with diagnostically relevant cytogenetic, molecular, and immunohistochemical testing methods.