Molecular Marker Testing Research Articles

QTL Mapping for Adult-Plant Resistance to Leaf Rust in Italian Wheat Cultivar Libellula.

Wheat leaf rust (Lr), which is caused by Puccinia triticina Eriks. (Pt), is one of the most important wheat diseases affecting wheat production globally. Using resistant wheat cultivars is the most economical and environmentally friendly way to control leaf rust. The Italian wheat cultivar Libellula has demonstrated good resistance to Lr in field studies. To identify the genetic basis of Lr resistance in 'Libellula', 248 F6 recombinant inbred lines from the cross 'Libellula'/'Huixianhong' was phenotyped for Lr severity in seven environments: the 2014/2015, 2016/2017, 2017/2018, and 2018/2019 cropping seasons at Baoding, Hebei Province, and the 2016/2017, 2017/2018, and 2018/2019 crop seasons at Zhoukou, Henan Province. Bulked segregant analysis and simple sequence repeat markers were then used to identify the quantitative trait loci (QTLs) for Lr adult-plant resistance in the population. Six QTLs were consequently detected and designated as QLr.hebau-1AL and QLr.hebau-1AS that were presumed to be new and QLr.hebau-1BL, QLr.hebau-3AL, QLr.hebau-4BL, and QLr.hebau-7DS that were identified at similar physical positions as previously reported QTLs. Based on chromosome positions and molecular marker tests, QLr.hebau-1BL and QLr.hebau-7DS share similar flanking markers with Lr46 and Lr34, respectively. Lr46 and Lr34 are race nonspecific adult plant resistance (APR) genes for leaf rust and stripe rust and powdery mildew. QLr.hebau-4BL showed multiple disease resistance to leaf rust, stripe rust, Fusarium head blight, and powdery mildew. The QTL identified in this study, as well as their closely linked markers, may potentially be used in marker-assisted selection in wheat breeding.

The Chinese Society of Clinical Oncology (CSCO): Clinical guidelines for the diagnosis and treatment of gastric cancer, 2023.

The 2023 update of the Chinese Society of Clinical Oncology (CSCO) Clinical Guidelines for Gastric Cancer focuses on standardizing cancer diagnosis and treatment in China, reflecting the latest advancements in evidence-based medicine, healthcare resource availability, and precision medicine. These updates address the differences in epidemiological characteristics, clinicopathological features, tumor biology, treatment patterns, and drug selections between Eastern and Western gastric cancer patients. Key revisions include a structured template for imaging diagnosis reports, updated standards for molecular marker testing in pathological diagnosis, and an elevated recommendation for neoadjuvant chemotherapy in stage III gastric cancer. For advanced metastatic gastric cancer, the guidelines introduce new recommendations for immunotherapy, anti-angiogenic therapy and targeted drugs, along with updated management strategies for human epidermal growth factor receptor 2 (HER2)-positive and deficient DNA mismatch repair (dMMR)/microsatellite instability-high (MSI-H) patients. Additionally, the guidelines offer detailed screening recommendations for hereditary gastric cancer and an appendix listing drug treatment regimens for various stages of gastric cancer. The 2023 CSCO Clinical Guidelines for Gastric Cancer updates are based on both Chinese and international clinical research and expert consensus to enhance their applicability and relevance in clinical practice, particularly in the heterogeneous healthcare landscape of China, while maintaining a commitment to scientific rigor, impartiality, and timely revisions.

Molecular Marker Testing in Curable Non–Small Cell Lung Cancer—Practice Necessarily Precedes Data

This Viewpoint describes the use of broad molecular marker testing in patients with early-stage non–small cell lung cancer

ODP474 Critical Analysis of the Thyroid Cytopathologic Diagnosis of Atypia of Undetermined Significance and Associated Clinical Outcomes

Abstract Introduction FNA is the optimal test for classifying concerning thyroid nodules. Approximately 15-30% of FNAs are indeterminate, representing diagnostic challenge with intra- and inter-observer variability among cytologists. The Bethesda System (BS) for cytopathology was created in 2007 to standardize thyroid cytology with corresponding malignancy risk. Our goal is to identify the incidence of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/ FLUS) and the percent of malignant AUS/FLUS cases at our institution. Methods Chart review of 3068 adult patients with FNA performed from 2003 to 2015 was completed, with attention to reports considered "indeterminant". BS for reporting thyroid cytology was not in use at our institution during that time. Cytopathology reports were evaluated for key descriptors concerning for AUS, FLUS, or follicular neoplasm. Results 461 cytology reports included language consistent with possible "indeterminate" cytology. These reports were reviewed with our institution's cytopathologist and retrospectively assigned an equivalent BS category. 241 cases were consistent with BS category III (7.86% of all thyroid nodule FNAs done during this time period). Molecular marker studies were not being performed at our institution on indeterminate thyroid cytology specimens during this time period. Of the patients who had indeterminate cytology consistent with BS category III, 66.3% (160/241) went for surgery. The malignancy rate was 27.5% (44/160) in the BS category III group. Conclusion Our data demonstrated that category III nodules in some practice settings may have a higher risk of malignancy than traditionally believed, and that guidelines recommending repeat FNA or observation merit reconsideration. Molecular marker testing on indeterminate thyroid cytology specimens has been shown to be helpful in determining cases for surgery and is now being utilized at our institution. Presentation: No date and time listed

Molecular marker testing and reporting completeness for adult-type diffuse gliomas in the United States.

A newly developed brain molecular marker (BMM) data item was implemented by US cancer registries for individuals diagnosed with brain tumors in 2018-including IDH and 1p/19q-co-deletion statuses for adult-type diffuse gliomas. We thus investigated the testing/reporting completeness of BMM in the United States. Cases of histopathologically confirmed glioblastoma, astrocytoma, and oligodendroglioma diagnosed in 2018 were identified in the National Cancer Database. Adjusted odds ratios (ORadj) and 95% confidence intervals (CI) of BMM testing/reporting were evaluated for association with the selected patient, treatment, and facility-level characteristics using multivariable logistic regression. As a secondary analysis, predictors of MGMT promoter methylation testing/reporting among IDH-wildtype glioblastoma individuals were assessed. Key limitations of the BMM data item were that it did not include any details regarding testing technique or assay type and could not distinguish between a lack of testing and a lack of cancer registry reporting of testing results. Among 8306 histopathologically diagnosed adult-type diffuse gliomas nationally, overall BMM testing/reporting completeness was 81.1%. Compared to biopsy-only cases, odds of testing/reporting increased for subtotal (ORadj= 1.38 [95% CI: 1.20-1.59], P < .001) and gross total resection (ORadj=1.50 [95% CI: 1.31-1.72], P < .001). Furthermore, the odds were lowest at community centers (hospitals (67.3%; ORadj=0.35 [95% CI: 0.26-0.46], P < .001) and highest at academic/NCI-designated comprehensive cancer centers (85.4%; referent). By geographical location, BMM testing/reporting completeness ranged from a high of 86.8% at New England (referent) to a low of 76.0 % in the West South Central region (ORadj=0.57 [95% CI: 0.42-0.78]; P < .001). Extent of resection, Commission-on-Cancer facility type, and facility location were additionally significant predictors of MGMT testing/reporting among IDH-wildtype glioblastoma cases. Initial BMM testing/reporting completeness for individuals with adult-type diffuse gliomas in the United States was promising, although patterns varied by hospital attributes and extent of resection.

A Retrospective Study of Clinicopathologic Outcomes of Nodules With Hürthle Cell Cytology and the Thyroid Nodule App (TNAPP) Ultrasound Recommendations

ObjectivesHürthle cells are a common finding on thyroid fine-needle aspiration, but when they are the predominant cytology, they represent a difficult diagnostic challenge. The Thyroid Nodule App (TNAPP) is a new, publicly available web application utilizing ultrasound (US) features based on the updated 2016 American Association of Clinical Endocrinologists clinical practice guidelines for thyroid nodule management. This pilot study was performed to assess the TNAPP recommendations and surgical pathology outcomes of Hürthle cell-predominant thyroid nodules. MethodsA retrospective review of nodules with Bethesda III (atypia of undetermined significance with Hürthle cells) or Bethesda IV (suspicious for Hürthle cell neoplasm) cytology, for which surgery was performed between 2017 and 2021, was conducted. TNAPP US categories 1, 2, and 3 (low, intermediate, and high risk, respectively) were assigned based on nodule characteristics, and clinical management recommendations were recorded. Results were compared with histology-proven diagnoses. ResultsFifty-nine nodules in 57 patients where surgical pathology was available were analyzed with the TNAPP algorithm. Of the 59 nodules, 4 were US category 1 (low risk/suspicion), 40 were US category 2 (intermediate risk/suspicion), and 15 were US category 3 (high risk/suspicion). All US category 1 nodules were benign, while 30% of the US category 2 and 40% of the US category 3 nodules were malignant. Of the patients who had molecular marker testing with ThyroSeq, 22 out of 29 (76%) were positive, indicating either an intermediate or high risk of malignancy, 7 of which were malignant. ConclusionThis preliminary study suggests that TNAPP is a useful clinical tool for sonographic assessment of thyroid nodules with Hürthle cell cytology.

Mapping and characterization QTLs for phenological traits in seven pedigree-connected peach families

BackgroundEnvironmental adaptation and expanding harvest seasons are primary goals of most peach [Prunus persica (L.) Batsch] breeding programs. Breeding perennial crops is a challenging task due to their long breeding cycles and large tree size. Pedigree-based analysis using pedigreed families followed by haplotype construction creates a platform for QTL and marker identification, validation, and the use of marker-assisted selection in breeding programs.ResultsPhenotypic data of seven F1 low to medium chill full-sib families were collected over 2 years at two locations and genotyped using the 9 K SNP Illumina array. Three QTLs were discovered for bloom date (BD) and mapped on linkage group 1 (LG1) (172–182 cM), LG4 (48–54 cM), and LG7 (62–70 cM), explaining 17–54%, 11–55%, and 11–18% of the phenotypic variance, respectively. The QTL for ripening date (RD) and fruit development period (FDP) on LG4 was co-localized at the central part of LG4 (40–46 cM) and explained between 40 and 75% of the phenotypic variance. Haplotype analyses revealed SNP haplotypes and predictive SNP marker(s) associated with desired QTL alleles and the presence of multiple functional alleles with different effects for a single locus for RD and FDP.ConclusionsA multiple pedigree-linked families approach validated major QTLs for the three key phenological traits which were reported in previous studies across diverse materials, geographical distributions, and QTL mapping methods. Haplotype characterization of these genomic regions differentiates this study from the previous QTL studies. Our results will provide the peach breeder with the haplotypes for three BD QTLs and one RD/FDP QTL to create predictive DNA-based molecular marker tests to select parents and/or seedlings that have desired QTL alleles and cull unwanted genotypes in early seedling stages.

Quality of Life Following Molecular Marker Testing for Indeterminate Thyroid Nodules

Thyroid cancer has a disproportionately negative effect on the quality of life (QOL) compared to malignancies with a worse prognosis. The QOL of patients with indeterminate thyroid nodules has not been previously evaluated. We aimed to assess the impact of molecular test results on the QOL of patients with indeterminate thyroid nodules. A short version of the Thyroid-Related Patient-Reported Outcome (ThyPro-39) was used to assess the QOL of patients who underwent thyroid fine needle aspiration (FNA) biopsy throughout UCLA Health from May, 2016, to June, 2017. All patients with indeterminate biopsy results underwent molecular testing with either Afirma Gene Expression Classifier or ThyroSeq v2 at the time of the initial biopsy. The QOL associated with symptoms of goiter, anxiety, depression, and impaired daily life were analyzed. Of 825 consented patients, 366 completed the assessment (44.4% response rate). FNA results included 76% benign, 7% malignant, and 17% indeterminate. There were no differences in QOL between patients with a benign FNA and patients with an indeterminate result with benign molecular testing. In patients with an indeterminate FNA, symptoms of goiter (20.5 versus 10.4; P = .033) and depression (33.3 versus 21.0; P = .026) were worse for patients with suspicious versus benign molecular test results; however, no significant differences were observed in anxiety or impaired daily life. A benign molecular test result may provide reassurance for patients with indeterminate thyroid nodules that the risk of malignancy is low. Long-term follow-up is necessary to determine if benign molecular test results maintain improved QOL.

Identification and characterization of QTLs for fruit quality traits in peach through a multi-family approach

BackgroundFruit quality traits have a significant effect on consumer acceptance and subsequently on peach (Prunus persica (L.) Batsch) consumption. Determining the genetic bases of key fruit quality traits is essential for the industry to improve fruit quality and increase consumption. Pedigree-based analysis across multiple peach pedigrees can identify the genomic basis of complex traits for direct implementation in marker-assisted selection. This strategy provides breeders with better-informed decisions and improves selection efficiency and, subsequently, saves resources and time.ResultsPhenotypic data of seven F1 low to medium chill full-sib families were collected over 2 years at two locations and genotyped using the 9 K SNP Illumina array. One major QTL for fruit blush was found on linkage group 4 (LG4) at 40–46 cM that explained from 20 to 32% of the total phenotypic variance and showed three QTL alleles of different effects. For soluble solids concentration (SSC), one QTL was mapped on LG5 at 60-72 cM and explained from 17 to 39% of the phenotypic variance. A major QTL for titratable acidity (TA) co-localized with the major locus for low-acid fruit (D-locus). It was mapped at the proximal end of LG5 and explained 35 to 80% of the phenotypic variance. The new QTL for TA on the distal end of LG5 explained 14 to 22% of the phenotypic variance. This QTL co-localized with the QTL for SSC and affected TA only when the first QTL is homozygous for high acidity (epistasis). Haplotype analyses revealed SNP haplotypes and predictive SNP marker(s) associated with desired QTL alleles.ConclusionsA multi-family-based QTL discovery approach enhanced the ability to discover a new TA QTL at the distal end of LG5 and validated other QTLs which were reported in previous studies. Haplotype characterization of the mapped QTLs distinguishes this work from the previous QTL studies. Identified predictive SNPs and their original sources will facilitate the selection of parents and/or seedlings that have desired QTL alleles. Our findings will help peach breeders develop new predictive, DNA-based molecular marker tests for routine use in marker-assisted breeding.

Risk Stratification of Thyroid Nodules with Bethesda III Category: The Experience of a Territorial Healthcare Hospital.

BackgroundThe Bethesda System for Reporting Thyroid Cytolopathology (TBSRTC) is the standardized category-based reporting system for thyroid nodule (TN) aspirations; however, atypia of undetermined significance/follicular lesion of undetermined significance (Bethesda category III, AUS/FLUS) is the most controversial category. The aim of this study was to identify the degree of malignancy risk and the related risk factors in the surgical pathology of the Bethesda Category III thyroid nodules. MethodsA total of 4074 patients (15-90 years, 81.5% of females) were subjected to retrospective analysis, and a total of 463 nodules were classified as Bethesda Class III and included in the analysis. Once all the thyroid cytopathological slides and ultrasound (US) reports were reviewed, they were classified according to the Bethesda System for Reporting Thyroid Cytology, the American College of Radiology (ACR) and the Thyroid Imaging Reporting and Data System (TI-RADS).ResultsAmong the 463 Bethesda class III nodules, 167 nodules were surgically excised, showing an overall malignancy of 27.6% (n = 46/167). Patients having thyroid-stimulating hormone (TSH) levels of >4.5 mIU/L (35%), TN <2 cm (34.6%), solid or nearly solid (28.7%), highly hypoechoic (58.3%), longer than wide (50%), lobulated (45.5%), punctate echogenic (48.6%), ACR TI-RAD 5 (55.2%) and falling under the ATA category of high suspicion (50%), displayed a higher risk of malignancy (ROM). The chi-square test revealed a strong association between the echogenicity, echogenic foci, ACR TI-RAD and American Thyroid Association (ATA) category between the malignant and benign nodules. The papillary thyroid carcinoma (PTC) follicular variant (39%) and PTC classical (27%) were identified, in this study population, as the commonest forms of thyroid cancer.ConclusionThe nodules with AUS/FLUS cytology malignancy rate are comparable with the earlier estimations of other countries. The ACR TI-RAD displayed more accurate diagnostic performances in predicting malignancy in the Bethesda III nodules. However, to confirm the accuracy of the molecular marker tests in specific cytological scenarios, more extensive studies are required in the future.

Long-Term Outcomes of Thyroid Nodule AFIRMA GEC Testing and Literature Review: An Institutional Experience.

To assess outcomes of thyroid nodules analyzed with the AFIRMA gene expression classifier (GEC) and to perform a comprehensive literature review. Retrospective analysis of patients with thyroid nodules who underwent AFIRMA GEC testing at our institution. A tertiary care academic institution. We collected clinical outcomes for 416 thyroid nodules that were analyzed with AFIRMA GEC between 2011 and 2015, including long-term follow-up through 2019. We performed a comprehensive literature review. The resection rate for nodules with "suspicious" GEC results was 85% with a positive predictive value of 37%. The resection rate for nodules with "benign" GEC results was 24% with a negative predictive value of 90%. The prevalence of thyroid malignancy in patients with thyroid nodules with indeterminate cytology at our institution during this timeframe was 41%, thus lowering our negative predictive value. Mean follow-up duration for unresected nodules was 27.8 months. Our resection rates for nodules with "benign" GEC were among the highest reported in the literature. Molecular marker testing of thyroid nodules with indeterminate cytology can aid in the surgical decision making by obviating the need for diagnostic surgery and/or guiding extent of resection. Patients with other indications for surgery may not benefit from such costly testing.

Clinical Molecular Marker Testing Data Capture to Promote Precision Medicine Research Within the Cancer Research Network.

To evaluate health care systems for the availability of population-level data on the frequency of use and results of clinical molecular marker tests to inform precision cancer care. We assessed cancer-related molecular marker test data availability across 12 US health care systems in the Cancer Research Network. Overall, these systems provide care to a diverse population of more than 12 million people in the United States. We performed qualitative analyses of test data availability for five blood-based protein, nine germline, and 14 tissue-based tumor marker tests in each health care system's electronic health record and tumor registry using key informants, test code lists, and manual review of data types and output. We then performed quantitative analyses to estimate the proportion of patients with cancer with test utilization data and results for specific molecular marker tests. Health systems were able to systematically capture population-level data on all five blood protein markers, six of 14 tissue-based tumor markers, and none of the nine germline markers. Successful, systematic data capture was achievable for tests with electronic data feeds for test results (blood protein markers) or through prior manual abstraction by tumor registrars (select tumor-based markers). For test results stored in scanned image files (particularly germline and tumor marker tests), information on which test was performed and test results was not readily accessible in an electronic format. Even in health care systems with sophisticated electronic health records, there were few codified data elements available for evaluating precision cancer medicine test use and results at the population level. Health care organizations should establish standards for electronic reporting of precision medicine tests to expedite cancer research and facilitate the implementation of precision medicine approaches.

PERFORMANCE OF 19-GAUGE NEEDLE DURING EBUS-TBNA IN THE DIAGNOSIS AND TESTING OF MOLECULAR MARKERS IN LUNG CANCER

SESSION TITLE: Wednesday Electronic Posters 4 SESSION TYPE: Original Inv Poster Discussion PRESENTED ON: 10/23/2019 09:45 AM - 10:45 AM PURPOSE: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has become the standard for diagnosis and staging of lung cancer. Needle aspirates of mediastinal lymph nodes can provide cytologic diagnosis as well as specific tumor biomarkers that provide important information to guide targeted therapy. Historically 21-gauge and 22-gauge needles have been paired with EBUS. We evaluated the performance of EBUS-TBNA using a 19-gauge needle in the assessment of tumor tissue obtained and success of testing for molecular markers. METHODS: We prospectively enrolled adult patients with mediastinal lymphadenopathy concerning for metastatic lung cancer in two academic medical centers. Patients underwent diagnostic EBUS-TBNA utilizing 19-gauge needles. All cases were evaluated with on-site cytology and cell blocks were prepared and evaluated by pathology. Cases of non-small cell lung cancer (NSCLC) were evaluated for presence of PD-L1. Cases of Adenocarcinoma were evaluated for three molecular markers: EGFR, ROS-1, and ALK. RESULTS: Fifty patients were enrolled and had the following cancer diagnoses: 32% with adenocarcinoma, 30% with small cell cancer, 26% with squamous cell carcinoma, 6% with undifferentiated NSCLC, 4% with other types of pulmonary cancers and 2% with carcinoma of unknown primary. Average number of needle passes was 5. Block quality was judged by total number of tumor cells per H&E stained slide of each cell block (58% of specimens had >500 cells and 22% had 200-500 cells), average number of tumor cells in 10 high power fields of the area containing the highest number of tumor cells (84% of specimens had more than 30 tumor cells) and percentage of tumor DNA in area selected for molecular analysis (62% had >40% and 10% had 21-40%) PD-L1 assay was successfully performed in 28 out of 31 NSCLC cases (90%). Of those cases, 68% demonstrated positive expression. In adenocarcinoma cases, the specimen adequacy for molecular marker testing was 90%. The success rate in testing was 90% for EGFR and 86% for ALK. For ROS-1, the success rate for testing was 67% (14 out of 21) while 24% of the specimens (5 out of 21) were deemed to have adequate tumor tissue but experienced technical difficulty with the assay. There were no adverse events. CONCLUSIONS: EBUS-TBNA using 19-gauge needles can obtain a high number of tumor cells and has a high rate of success in performing assays of PD-L1, EGFR, and ALK in non-small cell lung cancer patients without an increase in adverse events. The success rate of ROS-1 testing was lower. CLINICAL IMPLICATIONS: EBUS-TBNA of mediastinal lymphadenopathy with 19-gauge needle can suffice as a less invasive means to collect tumor cells and determine molecular marker status in patients with lung cancer. Larger comparative trials are needed. DISCLOSURES: Consultant relationship with Olympus Please note: $5001 - $20000 Added 11/25/2018 by Alexander Chen, source=Web Response, value=Consulting fee Consultant relationship with Auris Please note: $1001 - $5000 Added 11/25/2018 by Alexander Chen, source=Web Response, value=Consulting fee Consultant relationship with Intuitive Surgical Please note: $1001 - $5000 Added 11/25/2018 by Alexander Chen, source=Web Response, value=Consulting fee Consultant relationship with Boston Scientific Please note: $1001 - $5000 Added 11/25/2018 by Alexander Chen, source=Web Response, value=Consulting fee Research relationship with Veran Medical Please note: $5001 - $20000 Added 03/14/2019 by Alexander Chen, source=Web Response, value=Grant/Research Owner/Founder relationship with Restore3D Please note: $5001 - $20000 Added 11/27/2018 by George Cheng, source=Web Response, value=Ownership interest Consultant relationship with Medtronic Please note: $1-$1000 Added 11/27/2018 by George Cheng, source=Web Response, value=Consulting fee Research relationship with Intuitive Surgical Please note: $20001 - $100000 Added 11/27/2018 by George Cheng, source=Web Response, value=Grant/Research Consultant relationship with Boston Scientific Please note: $1001 - $5000 Added 11/27/2018 by George Cheng, source=Web Response, value=Consulting fee Speaker/Speaker's Bureau relationship with Pinnacle Biologics Please note: $1-$1000 Added 11/27/2018 by George Cheng, source=Web Response, value=Honoraria Research relationship with Veran Please note: $1001 - $5000 Added 11/27/2018 by George Cheng, source=Web Response, value=Grant/Research Support No relevant relationships by Kevin Davidson, source=Web Response No relevant relationships by Coral Giovacchini, source=Web Response No relevant relationships by Claudia Jones, source=Web Response No relevant relationships by Rachel Jug, source=Web Response No relevant relationships by Kamran Mahmood, source=Web Response no disclosure on file for elizabeth pavlisko; no disclosure on file for Scott Shofer; No relevant relationships by Momen Wahidi, source=Web Response no disclosure on file for Cody Weimholt; No relevant relationships by Zhongren Zhou, source=Web Response

Endobronchial ultrasound-guided intranodal forceps biopsy (EBUS-IFB)-technical review.

Endobronchial ultrasound (EBUS) and transbronchial needle aspiration (TBNA) have changed the landscape of pulmonology. Mediastinal structures beyond the confines of airway walls are visualized in real-time with EBUS, leading to improved accuracy of tissue sampling and diagnostic yield. With the development of various needle sizes ranging from 25-G to 19-G, the sampling of lymph nodes is becoming easier and more commonplace. Yet, certain conditions such as sarcoidosis and lymphoma may still be difficult to diagnose via EBUS-TBNA. Furthermore, in the age of targeted therapy, there are more demands on EBUS-TBNA samples for molecular marker testing and next-generation sequencing. Here, we present a complementary methodology, EBUS-guided intranodal forceps biopsy (EBUS-IFB), for tissue acquisition that may help address these deficiencies. Specifically, we aim to propose indications, contraindications, outline approaches in performing IFB, and provide an overview of the data for this complementary technique.

Electrochemical detection and screening of bladder cancer recurrence using direct electrochemical analysis of urine: A non-invasive tool for diagnosis

Although detection of urothelial cell carcinoma (or bladder cancer, BC) can be performed via cytological, molecular and genetic marker tests on urine, cystoscopy, an invasive technique, still remains as the gold methodology in clinical practice. It is presented a non-invasive method for detecting BC recurrence consisting of a direct electrochemical test in urine combining voltammetric data at gold and glassy carbon electrodes. The diagnosis is based on the ratio between characteristic voltammetric features recorded for tryptophan, serotonin and melatonin and other related metabolites. The method was tested by means of a clinical trial with 30 patients diagnosed of bladder cancer and a two control groups: 17 healthy volunteers and 15 patients diagnosed of other urinary pathologies and permitted detection of non-muscle invasive stages (pTa, pT1) and muscle-invasive stages (pT2 cancers) of BC.

Prioritizing molecular markers to test for in the initial workup of advanced non-small cell lung cancer: wants versus needs.

The current standard of care for molecular marker testing in patients with advanced non-small cell lung cancer (NSCLC) has been evolving over several years and is a product of the quality of the evidence supporting a targeted therapy for a specific molecular marker, the pre-test probability of that marker in the population, and the magnitude of benefit seen with that treatment. Among the markers that have one or more matched targeted therapies, only a few are in the subset for which they should be considered as most clearly worthy of prioritizing to detect in the first line setting in order to have them supplant other first line alternatives, and in only a subset of patients, as defined currently by NSCLC histology. Specifically, this currently includes testing for an activating epidermal growth factor receptor (EGFR) mutation or an anaplastic lymphoma kinase (ALK) or ROS1 rearrangement. This article reviews the history and data supporting the prioritization of these markers in patients with non-squamous NSCLC, a histologically selected population in whom the probability of these markers combined with the anticipated efficacy of targeted therapies against them is high enough to favor these treatments in the first line setting. In reviewing the evidence supporting this very limited core subset of most valuable molecular markers to detect in the initial workup of such patients, we can also see the criteria by which other actionable markers need to reach in order to be widely recognized as reliably valuable enough to warrant prioritization to detect in the initial workup of advanced NSCLC as well.

Quantitative trait loci mapping of adult‐plant resistance to leaf rust in a Fundulea 900 × ‘Thatcher’ wheat cross

AbstractWheat leaf rust (LR), caused by the obligate biotrophic fungus Puccinia triticina (Pt), is a destructive foliar disease of common wheat (Triticum aestivum L.) worldwide. The most effective, economic means to control the disease is resistant cultivars. The Romanian wheat line Fundulea 900 showed high resistance to LR in the field. To identify the basis of resistance to LR in Fundulea 900, a population of 188 F2:3 lines from the cross Fundulea 900/‘Thatcher’ was phenotyped for LR severity during the 2010–2011, 2011–2012 and 2012–2013 cropping seasons in the field at Baoding, Hebei Province. Bulked segregant analysis and simple sequence repeat markers were used to identify the quantitative trait loci (QTLs) for LR adult‐plant resistance in the population. Three QTLs were detected and designated as QLr.hebau‐1BL, QLr.hebau‐2DS and QLr.hebau‐7DS. Based on the chromosome positions and molecular marker tests, QLr.hebau‐1BL is Lr46, and QLr.hebau‐7DS is Lr34. QLr.hebau‐2DS was derived from ‘Thatcher’ and was close to Lr22. This result suggests that Lr22b may confer residual resistance on field nurseries when challenged with isolates virulent on Lr22b, or another gene linked to Lr22b confers this resistance from ‘Thatcher’. This study confirms the value of Lr34 and Lr46 in breeding for LR resistance in China; the contribution of the QTL to chromosome 2D needs further validation.

Patterns of diagnostic marker assessment in adult diffuse glioma: a survey of the European Confederation of Neuropathological Societies (Euro-CNS).

The 2016 update of the WHO classification has introduced an integrated diagnostic approach that incorporates both tumor morphology and molecular information. This conceptual change has far-reaching implications, especially for neuropathologists who are in the forefront of translating molecular markers to routine diagnostic use. Adult diffuse glioma is a prototypic example for a group of tumors that underwent substantial regrouping, and it represents a major workload for surgical neuropathologists. Hence, we conducted a survey among members of the European Confederation of Neuropathological Societies (Euro-CNS) in order to assess 1) the extent to which molecular markers have already been incorporated in glioma diagnoses, 2) which molecular techniques are in daily use, and 3) to set a baseline for future surveys in this field. Based on 130 responses from participants across 40 nations neuropathologists uniformly rate molecular marker testing as highly relevant and already incorporate molecular information in their diagnostic assessments. At the same time however, the survey documents substantial differences in access to crucial biomarkers and molecular techniques across geographic regions and within individual countries. Concerns are raised concerning the validity of test assays with MGMT, 1p19q, and ATRX; being perceived as most problematic. Neuropathologists advocate the need for international harmonization of standards and consensus guidelines, and the majority is willing to actively engage in interlaboratory trials aiming at quality control (Figure 1).

Application of RNA isolating system in blood molecular marker tests

As one important member of the biological sample library, blood samples are rich in biological molecules, which can be used for disease diagnosis, prognosis of disease staging, and prognosis et al. compared with tissue samples, blood samples have some advantages, such as easier to access, sampling in a row and rich test items and so on. However, after blood samples were collected, which need to be processed, packed and frozen in ice for long-term preservation container. Otherwise RNA in the blood sample is unstable and easily degradation in normal temperature transportation and preservation condition, thus subsequently affecting the molecular diagnostic biomarkers' detection, analysis, research and development. In this paper, This review summarizes the current clinical and research work of routine blood collection and preservation methods effecting on blood RNA degradation and solution for avoiding these degrading which can help testing changings of blood biomarker more accurately.(Chin J Lab Med, 2016, 39: 559-561) Key words: Biomarker; Blood sample; Blood collection system; Ribonucleic acid

Molecular-Directed Treatment of Differentiated Thyroid Cancer: Advances in Diagnosis and Treatment.

Thyroid cancer incidence is increasing, and when fine-needle aspiration biopsy results are cytologically indeterminate, the diagnosis is often still established only after thyroidectomy. Molecular marker testing may be helpful in guiding patient-oriented and tailored management of thyroid nodules and thyroid cancer. To summarize available data on the use of molecular testing to improve the diagnosis and prognostication of thyroid cancer. A MEDLINE review was conducted using the primary search terms molecular, thyroid cancer, thyroid nodule, and gene expression classifier in search strings. Articles were restricted to those published between January 1, 2010, and June 1, 2015, inclusive of adult humans, and reported in the English language only. Of 867 titles screened, 67 articles were further identified for review of the full text. The 2 most studied molecular marker testing techniques for indeterminate thyroid nodules include gene expression classifier analysis and evaluation for somatic mutations or rearrangements that are commonly found in thyroid cancer (7-gene panel). Nodules with benign results on gene expression classifier analysis can be associated with less than a 5% risk of cancer and may be observed, while nodules with positive results on the 7-gene panel may have a higher risk of cancer (80%-100%) and definitive surgery can be recommended. However, cancer prevalence and geographic variations in histologic subtypes may affect accuracy and clinical applicability of both tests. Molecular marker tests such as ThyroSeq version 2.1 are more comprehensive, but they need further validation. Preoperative risk stratification using molecular markers also may be used to better define the optimal extent of thyroidectomy for patients with thyroid cancer. Molecular markers potentially can augment the diagnostic specificity of fine-needle aspiration biopsy to better differentiate cytologically indeterminate nodules that can be safely observed from cytologically indeterminate nodules that may be associated with differentiated thyroid cancer. Long-term follow-up data are still needed; in the end, patient preference regarding the relative risks and benefits of molecular testing is at the crux of decision making.