Cancer Genetics最新文献_第3页

59. What the TERT? - A telomerase reverse transcriptase case study 59.什么是 TERT？- 端粒酶逆转录酶案例研究

IF 1.4 4区医学

Cancer Genetics Pub Date : 2024-08-01 DOI: 10.1016/j.cancergen.2024.08.061

{"title":"59. What the TERT? - A telomerase reverse transcriptase case study","authors":"","doi":"10.1016/j.cancergen.2024.08.061","DOIUrl":"10.1016/j.cancergen.2024.08.061","url":null,"abstract":"<div><div>Telomerase reverse transcriptase is a catalytic subunit of the telomerase protein that is involved in the maintenance of genomic stability. <em>TERT</em> aberrations are important biomarkers in the diagnosis, prognosis, and treatment of many human cancers. The <em>TERT</em> promoter has proven to be a difficult region of testing amongst a variety of currently available technologies.</div><div><em>TERT</em> promoter mutation analysis was performed on brain tissue of a 62-year old male meningioma patient using MALDI-TOF (Agena Bioscience MassARRAY platform) and detected a low frequency <em>TERT</em> mutation. The pathologist questioned the result and sent some of the sample for additional testing to 2 different referral laboratories - one aliquot was sent for Pyrosequencing and the other for NGS - both with a higher limit of detection than MALDI-TOF. Neither methodology detected a <em>TERT</em> mutation. On the basis of these result the diagnosis was changed.</div><div>Certain of our <em>TERT</em> mutation, an aliquot of the remaining extracted DNA was sent for digital droplet PCR (ddPCR) which has the same limit of detection as our MALDI-TOF platform. A <em>TERT</em> mutation was confirmed.</div><div>This case highlights the challenges in <em>TERT</em> promoter mutation analysis as well as the significance of confirmatory testing. The importance of confirming results using platforms with an appropriate limit of detection is paramount in reducing under-reporting of low level mutations of clinical significance.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142323472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

43. Challenges of classifying variants associated with disorders of somatic mosaicism and guideline creation 43.体细胞嵌合紊乱相关变异的分类挑战与准则制定

IF 1.4 4区医学

Cancer Genetics Pub Date : 2024-08-01 DOI: 10.1016/j.cancergen.2024.08.045

{"title":"43. Challenges of classifying variants associated with disorders of somatic mosaicism and guideline creation","authors":"","doi":"10.1016/j.cancergen.2024.08.045","DOIUrl":"10.1016/j.cancergen.2024.08.045","url":null,"abstract":"<div><div>Disorders of somatic mosaicism (DoSM) constitute rare genetic disorders characterized by post-zygotic events leading to segmental distribution of disease. The early presentation of associated phenotypes often mimics germline diseases, complicating molecular diagnosis. Additionally, current guidelines from the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) focus specifically on germline and cancer variants, complicating the interpretation of DoSM-associated somatic variation. The ClinGen Brain Malformation Expert Panel guidelines have created valuable updates to account for brain-specific disorders of somatic mosaicism, but their applicability to the diverse DoSM presentations is limited. At Washington University School of Medicine, we have identified shortcomings in applying ACMG/AMP germline guidelines to DoSM variants, prompting the development of DoSM-specific variant interpretation guidelines. Leveraging our laboratory's extensive experience in somatic variation interpretation, we have developed DoSM guidelines that are applicable across genes and clinical contexts pertinent to non-cancerous somatic testing. These guidelines address the critical need for accurate somatic variant interpretation in DoSM, where treatment advances hinge on understanding the overlap between somatic variants in DoSM and tumors. This comprehensive framework addresses the gap in existing guidelines, offering an iinvaluable resource for clinical laboratories engaged in non-cancerous somatic testing and advancing precision medicine for patients with DoSM. We will present the developed guidelines, discuss challenges specific to DoSM and criteria development, and interesting cases studies where DoSM-specific guidelines were critical to accurate diagnosis.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142323297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

66. Prognostic impact of genomic testing results in patients undergoing transplantation for myelofibrosis 66.基因组检测结果对骨髓纤维化移植患者预后的影响

IF 1.4 4区医学

Cancer Genetics Pub Date : 2024-08-01 DOI: 10.1016/j.cancergen.2024.08.068

{"title":"66. Prognostic impact of genomic testing results in patients undergoing transplantation for myelofibrosis","authors":"","doi":"10.1016/j.cancergen.2024.08.068","DOIUrl":"10.1016/j.cancergen.2024.08.068","url":null,"abstract":"<div><div>Despite its known superior detection rate for chromosomal anomalies compared to karyotype and FISH studies, Chromosome Genomic Array Testing (CGAT) is not used as a routine clinical test for myelofibrosis. We investigated the prognostic significance of CGAT and mutation results by NGS in myelofibrosis patients who underwent hematopoietic cell transplantation between 2000 and 2017 at our center (n=44). CGAT was done in a CLIA lab using CytoScanHD (ThermoFisher). NGS was performed either in a CLIA lab using UW Heme Gene Panel by NGS (n=9) or retrospectively at a research lab using TruSight myeloid panel (Illumina, n=35). Twenty-four patients (55%) had abnormal CGAT results. In 18 patients (41%), CGAT uniquely demonstrated cnLOH, with 9p cnLOH being the most frequent (n=8, 18%). Thirty-five patients had myeloproliferative neoplasm (MPN) driver mutations: 17 (39%) <em>JAK2</em> pV617F, 16 (36%) <em>CALR</em> exon 9 mutation, and two <em>MPL</em> pW515 (5%). With a median of 91 (range 2-258) months of follow-up, event-free survival (EFS; event referring to relapse) was 59%, and overall survival (OS) was 68%. Abnormal CGAT results (n=24, P=0.03), <em>U2AF1</em> mutation (n=5, P=0.028) and 1q gain (n=3, P=0.009) were associated with worse EFS. The genetic aberrations had no significant effect on OS in this cohort. <em>ASXL1</em> mutations (n=14) appeared to associate with a later onset of chronic graft-versus-host-disease (P=0.03). In conclusion, assessments by both CGAT and NGS pre-transplantation provide valuable outcome information and may be considered as routine clinical testing for myelofibrosis</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142323397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

39. Modifying cancer variant interpretation guidelines for the curation of histone H3 variants: The 'next step' of the Cl 39.修改癌症变异体解释指南，用于组蛋白 H3 变异体的整理：组蛋白 H3 变异的 "下一步

IF 1.4 4区医学

Cancer Genetics Pub Date : 2024-08-01 DOI: 10.1016/j.cancergen.2024.08.041

{"title":"39. Modifying cancer variant interpretation guidelines for the curation of histone H3 variants: The 'next step' of the Cl","authors":"","doi":"10.1016/j.cancergen.2024.08.041","DOIUrl":"10.1016/j.cancergen.2024.08.041","url":null,"abstract":"<div><div>Histone H3 variants pose numerous challenges for curation due to varied nomenclature for their isoforms and encoding genes. These are further compounded by the tumor-specific settings in which histone H3 variants occur. Therefore, the Histone H3 SC-VCEP aimed to adapt and modify the ClinGen/CGC/VICC Oncogenicity SOP and AMP/ASCO/CAP guidelines for the interpretation of H3 variants specific to diffuse midline glioma, H3 K27-altered and diffuse hemispheric glioma, H3 G34-mutant.</div><div>The main proposed specifications to the ClinGen/CGC/VICC Oncogenicity SOP include: (1) the incorporation of trimethylation loss at the K27 residue and functional studies at G34 into evidence code OS2 and (2) stipulation of location at a 'conserved residue affecting epigenetic modification (e.g. histone H3 K27, G34, or K36)' for evidence code OM1.</div><div>The main proposed modifications to the ClinGen/CGC/VICC Oncogenicity SOP include: (1) an 'OS1_moderate' criterion (2 points), allowing for the same amino acid change as a previously established oncogenic variant in a homologous H3 gene; (2) an 'OS2_supportive' criterion (1 point), incorporating supportive evidence of frequent co-occurring variants (e.g. TP53, PDGFRA, ACVR1) or other supportive evidence of histone H3 mutation (e.g. gene expression analysis); and (3) an alternate OP2 criterion (1 point) applied when clinicopathologic features align with a corresponding histone mutant glioma in the WHO Classification. This novel modification introduces clinicopathological correlation into the assessment of oncogenicity. Evidence specifications have also been made to the AMP/ASCO/CAP guidelines.</div><div>Evaluation of our proposed changes to the guidelines is underway in a defined set of pilot variants.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142323293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

52. A ClinGen Somatic curation effort focused on EGFR variants 52.ClinGen 体系整理工作侧重于表皮生长因子受体变异

IF 1.4 4区医学

Cancer Genetics Pub Date : 2024-08-01 DOI: 10.1016/j.cancergen.2024.08.054

{"title":"52. A ClinGen Somatic curation effort focused on EGFR variants","authors":"","doi":"10.1016/j.cancergen.2024.08.054","DOIUrl":"10.1016/j.cancergen.2024.08.054","url":null,"abstract":"<div><div>As next generation sequencing becomes a routine part of clinical diagnostic and follow up workup for tumor assessment, consensus on cancer variant interpretation and expanded knowledgebase curation is needed. <em>EGFR</em> (Epidermal Growth Factor Receptor) is a well recognized oncogene and <em>EGFR</em> SNVs, CNVs, indels, and fusions have important predictive, diagnostic, and prognostic roles in a variety of cancer types. A definitive collection of tumor-specific <em>EGFR</em> somatic variants and their responses to FDA-approved EGFR inhibitors has not yet been assembled and <em>EGFR</em>-specific guidelines for defining variant oncogenicity have not been proposed. Due to their growing clinical relevance, the ClinGen Somatic Clinical Domain Working Group Solid Tumor Taskforce (STTf) performed a pilot curation effort on 15 <em>EGFR</em> fusions, and a number of curation challenges were noted. For instance, <em>EGFR</em> fusions can be primary events in cancer or part of complex molecular alterations (e.g., involving amplification). The group will compile a list of EGFR fusions and collect data on characteristics such as genomic breakpoints, tumor-type associations, functional evidence, and sensitivity to inhibitors. We are forming an <em>EGFR</em> Somatic Cancer Variant Curation Expert Panel (<em>EGFR</em> SC-VCEP) to develop oncogenicity classification recommendations specific to <em>EGFR</em> fusions with future expansion to other <em>EGFR</em> sequence changes. The Step 1 ClinGen SC-VCEP application is in-progress for this effort. The results of this expert-led curation and the resulting guidelines will be publicly available through multiple avenues including the CIViC knowledgebase and ClinVar.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142322860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

62. Characterization of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) with KMT2A amplification 62.骨髓增生异常综合征（MDS）和急性髓性白血病（AML）KMT2A 扩增的特征描述

IF 1.4 4区医学

Cancer Genetics Pub Date : 2024-08-01 DOI: 10.1016/j.cancergen.2024.08.064

{"title":"62. Characterization of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) with KMT2A amplification","authors":"","doi":"10.1016/j.cancergen.2024.08.064","DOIUrl":"10.1016/j.cancergen.2024.08.064","url":null,"abstract":"<div><div><em>KMT2A</em> amplification is a rare high risk cytogenetic abnormality in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), which has been associated with complex karyotype, resistance to chemotherapy and higher frequency in elderly patients. Comprehensive elucidation of cytogenetic signatures in AML/MDS with <em>KMT2A</em> amplification, the subsequent clinical impact, as well as accompanying gene mutation profile would be beneficial for stratified patient care.</div><div>Herein, we present karyotyping/fluorescence in situ hybridization (FISH) data on 42 AML/MDS patients with <em>KMT2A</em> amplification, along with next generation sequencing (NGS) results and prognostic information in a subset of patients. The median age at diagnosis was 70 years. The male to female ratio was 1.8 (27:15). The median survival was 45 days. <em>KMT2A</em> amplification was identified by FISH. Chromosome analysis showed complex karyotype in all cases analyzed (n=38). The structural mechanisms associated with <em>KMT2A</em> amplification included homogeneously staining region (n=27), double minutes (n=6) and ring chromosome 11 (n=8). Deletions of 5q (64%) and 17p (62%) were the most common concurrent cytogenetic findings. Additional major concurrent cytogenetic abnormalities included loss of 7q (31%) and gain of chromosome 8 (29%). NGS results were available for 14 cases and <em>TP53</em> mutation was the most common alteration (n=12). Other mutations were detected in <em>TET2</em> (n=2), <em>NSD1</em> (n=2), <em>SAMD9L</em> (n=2), <em>DNMT3A</em> (n=1), <em>U2AF2</em> (n=1), <em>FLT3</em> (TKD, n=1), <em>NOTCH1</em> (n=1) and <em>SMC3</em> (n=1).</div><div>AML/MDS with <em>KMT2A</em> amplification is associated with poor outcome and specific concurrent cytogenetic and molecular abnormalities. Documenting additional data is valuable for improving the treatment landscape in these myeloid neoplasms.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142323478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

71. Validation of automated cell counter instruments for downstream cytogenetic testing 71.用于下游细胞遗传学检测的自动细胞计数器的验证

IF 1.4 4区医学

Cancer Genetics Pub Date : 2024-08-01 DOI: 10.1016/j.cancergen.2024.08.073

{"title":"71. Validation of automated cell counter instruments for downstream cytogenetic testing","authors":"","doi":"10.1016/j.cancergen.2024.08.073","DOIUrl":"10.1016/j.cancergen.2024.08.073","url":null,"abstract":"<div><div>Counting while blood cells (WBCs) from blood and bone marrow samples before culturing aids in standardizing workflows, yields, and quality of downstream testing in the cytogenetics laboratory. However, traditional cell counting methods are limited in speed and accuracy, prompting the search for a high-throughput, reliable replacement method. Here, we describe the results from validations of two automated fluorescent cell counting instruments (Cellaca MX and DeNovix CellDrop FL) for use in a high-throughput cytogenetics laboratory setting. These instruments utilize imaging cytometry principles and Acridine Orange/Propidium Iodide (AOPI) stains for assessing cellularity and viability assessment and do not require lysing of non-nucleated cells. Both instruments underwent validation incorporating a range of performance criteria including accuracy, precision, reagent stability, cellularity range, and cytogenetic culture (mitotic index) performance. The Cellaca MX was initially validated against a traditional Coulter counter, followed by the validation of the CellDrop FL compared to the Cellaca MX. Validation samples representing the clinical diagnostic encounter and with sufficient cellularity to set up concurrent cultures were counted using the clinical and test methods. A minimum of 10 samples were used for accuracy and internal volume/cellularity thresholds were evaluated. Concurrent cultures were evaluated for mitotic index following dropping and staining to assess quality. Ranges of cellularity used for inoculums were established to culture at 1M cells/mL. Both instruments have shown reliable operation across the full clinical range of sample cellularity. Our work shows automated fluorescent cell counting instruments employing AOPI stains can provide accurate and reproducible results in a high throughput setting.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142323481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

41. Step 2 updates for the oncogenic assessment of FLT3 variants by the ClinGen FLT3 somatic cancer variant curation expert 41.ClinGen FLT3 体癌基因变异整理专家对 FLT3 变异致癌评估的第二步更新

IF 1.4 4区医学

Cancer Genetics Pub Date : 2024-08-01 DOI: 10.1016/j.cancergen.2024.08.043

{"title":"41. Step 2 updates for the oncogenic assessment of FLT3 variants by the ClinGen FLT3 somatic cancer variant curation expert","authors":"","doi":"10.1016/j.cancergen.2024.08.043","DOIUrl":"10.1016/j.cancergen.2024.08.043","url":null,"abstract":"<div><div>Variant interpretation guidelines aid genetic professionals in assessing the strength of evidence for the variant pathogenicity and clinical significance. Currently, there are no standard guidelines for evaluation of <em>FLT3</em> variants, leading to variability in interpretation of <em>FLT3</em> tyrosine kinase and non-tyrosine kinase variants. The FLT3 Somatic Cancer Variant Curation Expert Panel (SC-VCEP), within the ClinGen Somatic Cancer CDWG, is actively developing the variant oncogenicity interpretation rules for the <em>FLT3</em> gene using ClinGen/CGC/VICC (PMID: <span><span>35101336</span><svg><path></path></svg></span>) to facilitate accurate classification of <em>FLT3</em> variants.</div><div>We will provide an update on the <em>FLT3</em>-specific modifications to evidence criteria OP1/SBP1 and OP4/SBS1. To address OP1/SBP1 we assessed multiple <em>in silico</em> prediction tools and their performance on FLT3-specific variants. Based on the analysis, we selected ClinPred and REVEL as optimal prediction tools for further evaluation during the pilot phase. We also modify the population allele frequency criteria for OP4/SBS1 using the spectrum of allele frequency of <em>FLT3</em> variants. Recognizing the need for applicability to internal tandem duplication (ITD) variants, the strength of OM2 has been increased to OM2_strong for this variant type. With these updates, all rules have been evaluated and modifications/specifications proposed for OVS1, OS2/SBS2, OS3/OM3/OP3, OM1, OM2, OP1/SBP1, OP2, SBVS1, and OP4/SBS1. Once approved, the validity of the rules will be assessed on a set of pilot variants.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142323295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

37. The clinical utility of the TSO500 clinically-verified test in patients with solid tumors: The Mayo Clinic experience 37.TSO500 临床验证检验对实体瘤患者的临床实用性：梅奥诊所的经验

IF 1.4 4区医学

Cancer Genetics Pub Date : 2024-08-01 DOI: 10.1016/j.cancergen.2024.08.039

{"title":"37. The clinical utility of the TSO500 clinically-verified test in patients with solid tumors: The Mayo Clinic experience","authors":"","doi":"10.1016/j.cancergen.2024.08.039","DOIUrl":"10.1016/j.cancergen.2024.08.039","url":null,"abstract":"<div><div>Clinical Laboratories reimbursement for large cancer panels has been challenging with many health care payers arguing about the clinical utility of such panels. We sought to investigate the clinical utility of the TSO500 kit in patients with solid tumors (ST) by determining its ability to detect a target for an FDA-approved drug in tumor type (FDA-in-TT), and in other tumor type (FDA-in-OTT).</div><div>The TSO500 kit which is commercially offered by Illumina company along with an analysis pipeline has been clinically verified in our laboratory and has been offered since 2021 for clinical care. A total of 1194 cases representing over 25 solid tumor types that were tested on the TSO500 platform were included in the study.</div><div>The top 3 indications for testing were lung cancer (35.6%), unknown primary (UNP) (14.5%), and other tumor types (12.5%). FDA-in-TT and FDA-in-OTT variants were identified in 531/1194(44.5%), and (257/1194)(15.4%), total (788/1194)(66%) cases, respectively. Immunotherapy markers including microsatellite instability (MSI-H) and/or high tumor mutation burden (TMB-H) were detected in 324 cases representing 60% of cases with FDA-in-TT and FDA-in-OTT, and 30% of all tested cases, respectively. Interestingly, 43/172(25%) of UKP cases had FDA-approved-drug, of which 35/43(81%) had TMB-H.</div><div>The detection of an FDA-in-TT and FDA-in-OTT target in 66% of patients, 60% of whom had TMB-H, a biomarker for FDA-approved immunotherapy drugs that requires interrogating over one megabase of the genome for accurate detection, provides strong evidence for the clinical utility of a large panels testing like the TSO500 in patients with solid tumors.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142323291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

57. Developing oncogenicity guidelines for BCR::ABL1-like B-lymphoblastic leukemia/lymphoma through expert consensus 57.通过专家共识制定 BCR::ABL1-类 B 淋巴细胞白血病/淋巴瘤致癌指南

IF 1.4 4区医学

Cancer Genetics Pub Date : 2024-08-01 DOI: 10.1016/j.cancergen.2024.08.059

{"title":"57. Developing oncogenicity guidelines for BCR::ABL1-like B-lymphoblastic leukemia/lymphoma through expert consensus","authors":"","doi":"10.1016/j.cancergen.2024.08.059","DOIUrl":"10.1016/j.cancergen.2024.08.059","url":null,"abstract":"<div><div>B-lymphoblastic leukemia/lymphoma (B-ALL) includes multiple distinct genetic subtypes. <em>BCR::ABL1-</em>like B-ALL is associated with high-risk disease with alterations impacting cytokine receptors and kinases that drive a gene expression profile which mimics <em>BCR::ABL1</em>-positive B-ALL. Given the significant genetic heterogeneity and various methodologies used to identify gene fusions, clinical diagnosis and decision-making for patients with this B-ALL subtype remain challenging.</div><div>Existing professional guidelines for <em>BCR::ABL1</em>-like B-ALL are not sufficiently detailed for consistent variant interpretation and routine practice between labs, which may impact both treatment decisions and clinical trial enrollment. To promote consensus, ClinGen has assembled a <em>BCR::ABL1</em>-like B-ALL Somatic Cancer Variant Curation Expert Panel (SC-VCEP) for variant interpretation related to this high-risk disease based on guidelines from the Somatic Cancer Clinical Domain Working Group.</div><div>Initially using <em>ABL1</em> fusions not involving BCR, we have drafted oncogenicity guidelines for fusions in this subtype of B-ALL. Adapting the NTRK SC-VCEP fusion guidelines we are evaluating fusion structure, cancer association, and functional evidence to support variant classification. To establish the scope of our pilot fusions for oncogenicity guidelines and AMP/ASCO/CAP categorization, we have expanded our evaluation to include other ABL-class genes (e.g., <em>ABL2, CSF1R</em>). These guidelines will be publicly available with finalized interpretations relevant to B-ALL. Ultimately, these efforts aim to provide community consensus related to the diagnostic, prognostic, and therapeutic implications of genetic changes in B-ALL.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142323474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0