Cancer Genetics最新文献_第4页

70. Acute myeloid leukemia with a novel AKAP9::PDGFRA fusion transformed from essential thrombocythemia 70.由原发性血小板增多症转化而来的新型 AKAP9::PDGFRA 融合急性髓性白血病

IF 1.4 4区医学

Cancer Genetics Pub Date : 2024-08-01 DOI: 10.1016/j.cancergen.2024.08.072

{"title":"70. Acute myeloid leukemia with a novel AKAP9::PDGFRA fusion transformed from essential thrombocythemia","authors":"","doi":"10.1016/j.cancergen.2024.08.072","DOIUrl":"10.1016/j.cancergen.2024.08.072","url":null,"abstract":"<div><div>Acute myeloid leukemia (AML) is a heterogeneous hematological malignancy associated with various combinations of gene mutations, epigenetic abnormalities, and chromosome rearrangement-related gene fusions. Despite the significant degree of heterogeneity in its pathogenesis, many gene fusions and point mutations are recurrent in AML and have been employed in risk stratification over the last several decades. Gene fusions have long been recognized for understanding tumorigenesis and their proven roles in clinical diagnosis and targeted therapies. Advances in DNA sequencing technologies and computational biology have contributed significantly to the detection of known fusion genes as well as for the discovery of novel ones. Several recurring gene fusions in AML have been linked to prognosis, treatment response, and disease progression. Here, we present a case with a long history of essential thrombocythemia and hallmark CALR mutation transforming to AML characterized by a previously unreported <em>AKAP9::PDGFRA</em> fusion gene. We propose mechanisms by which this fusion may contribute to the pathogenesis of AML and its potential as a molecular target for tyrosine kinase inhibitors.</div><div>Journal: Leukemia Research Reports</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":"142323480","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

72. What's under VarCat's hat: Modeling variant oncogenicity classifications with GA4GH Standards 72.VarCat 帽下有什么？利用 GA4GH 标准建立变体致癌性分类模型

IF 1.4 4区医学

Cancer Genetics Pub Date : 2024-08-01 DOI: 10.1016/j.cancergen.2024.08.074

{"title":"72. What's under VarCat's hat: Modeling variant oncogenicity classifications with GA4GH Standards","authors":"","doi":"10.1016/j.cancergen.2024.08.074","DOIUrl":"10.1016/j.cancergen.2024.08.074","url":null,"abstract":"<div><div>The Variation Categorizer (VarCat) is a tool for classifying variant oncogenicity for variant-disease pairings in a clinical laboratory workflow. VarCat implements the ClinGen/CGC/VICC oncogenicity guidelines to assist in the classification of a variant's capability for driving cancer formation and growth. VarCat provides an intuitive interface for structured data sharing and produces classification assessments compliant with genomic knowledge standards specified by the Global Alliance for Genomics and Health (GA4GH).</div><div>Here, we present the models, structures, and capabilities provided by VarCat's API and demonstrate its ability to create standardized assessments. VarCat leverages harmonized data from several genomic knowledge sources collated by the VICC MetaKB service. VarCat ensures comprehensive analysis by incorporating standardized gene, variant, therapeutic, disease, and evidence data, and it is driving the development of GA4GH genomic knowledge formats for oncogenicity data. We also describe the suite of normalization microservices used by MetaKB and VarCat to harmonize genomic knowledge concepts. We illustrate how VarCat reduces barriers to interoperable variant-associated evidence through the adoption of the GA4GH Variation Representation Specification (VRS). We also present standardized evidence data using the AMP/ASCO/CAP guidelines for clinical actionability. Overall, our work illustrates how GA4GH Genomic Knowledge Standards drive data interoperability and successful knowledge exchange, ultimately enhancing genetic disease comprehension and advancing patient care.</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":"142323331","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

31. A cross-consortia initiative for aligning the definitions and descriptions of gene fusions 31.统一基因融合定义和描述的跨联盟倡议

IF 1.4 4区医学

Cancer Genetics Pub Date : 2024-08-01 DOI: 10.1016/j.cancergen.2024.08.033

{"title":"31. A cross-consortia initiative for aligning the definitions and descriptions of gene fusions","authors":"","doi":"10.1016/j.cancergen.2024.08.033","DOIUrl":"10.1016/j.cancergen.2024.08.033","url":null,"abstract":"<div><div>Despite the well-established role of gene fusions in oncogenic processes, current practices for characterizing and annotating gene fusion events in the clinical setting and in biomedical literature are inconsistent. Consequently, evidence-based interpretation of functional and clinical significance of fusion variants requires laborious and time-consuming gathering and review of putative evidence. Differences between community standards inhibit the uniform communication of fusion events as well as the interoperability of tools, resources, and pipelines, ultimately impeding data sharing and downstream utility.</div><div>To address these challenges, a cross-consortia initiative between the Variant Interpretation for Cancer Consortium (VICC), CGC, ClinGen Somatic, and AMP was formed to develop a unified, standard nomenclature for representing the product of gene fusions (fusions.cancervariants.org). Invested participants across academic, government, and industry sectors engaged with these challenges to propose solutions via participation in community surveys and discussions to define and develop a standard for this diverse class of alterations. Our recent efforts to align these pre-release recommendations for fusion representation with the recommendations of the HGNC, ISCN, and HGVS nomenclature committees have resulted in consensus definitions and interoperable nomenclature systems for the description of gene fusions.</div><div>In January 2024, the first major release (21.0.0) of the HGVS nomenclature since 2020 includes the results of this work, which is also reflected in the cross-consortia recommendations. We discuss the vocabulary and nomenclature alignment between these related and cross-referenced standards, and provide recommendations for characterization and representation of gene fusions across these systems.</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":"142323395","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

20. FIP1L1::KIT fusion in a case of peripheral T-cell lymphoproliferative neoplasm responsive to tyrosine kinase inhibitor 20.对酪氨酸激酶抑制剂有反应的一例外周 T 细胞淋巴组织增生性肿瘤中的 FIP1L1::KIT 融合

IF 1.4 4区医学

Cancer Genetics Pub Date : 2024-08-01 DOI: 10.1016/j.cancergen.2024.08.022

{"title":"20. FIP1L1::KIT fusion in a case of peripheral T-cell lymphoproliferative neoplasm responsive to tyrosine kinase inhibitor","authors":"","doi":"10.1016/j.cancergen.2024.08.022","DOIUrl":"10.1016/j.cancergen.2024.08.022","url":null,"abstract":"<div><div>Myeloid/lymphoid neoplasms with eosinophilia and defining gene rearrangements commonly involve <em>FIP1L1::PDGFRA</em>. Eosinophilia is not an invariable feature. Neoplastic myeloid/lymphoid populations may be present at the same or different sites, with T-cell neoplasms being the conventional lymphoid component.</div><div>The case involves a 43-year-old male with chronic intractable disseminated skin rashes. Blood flow cytometry showed an aberrant T-cell population with no surface CD3 expression. Atypical T-cell infiltrates were present in the bone marrow, skin, and inguinal lymph node biopsy, and clonal <em>TRG</em> rearrangements were detected in blood, skin, and lymph node. However, there were no specific features to definitively classify the abnormal T-cell infiltrates. Bone marrow was fibrotic and hypercellular with only focal eosinophilia. Next-generation sequencing of blood and lymph node detected no significant mutations, and bone marrow cells demonstrated a normal karyotype. Fluorescence in situ hybridization demonstrated loss of both the <em>CHIC2</em> and <em>PDGFRA</em> signals, with retention of the <em>FIP1L1</em> signal. Whole-genome microarray analysis revealed an ∼1.3 Mb loss in the 4q12 region with breakpoints within the <em>FIP1L1</em> and <em>KIT</em> genes. A novel <em>FIP1L1::KIT</em> fusion was confirmed by RNA-sequencing demonstrating in-frame retention of the <em>KIT</em> tyrosine kinase domain. The patient had a poor response to chemotherapy but superb response to the tyrosine kinase inhibitor, dasatinib.</div><div><em>FIP1L1::KIT</em> fusion has not been described in systemic peripheral T-cell neoplasms without significant abnormality in myeloid lineage. This case indicates that <em>KIT</em> fusions are targetable genetic lesions and supports the inclusion of <em>KIT</em> fusions in the myeloid/lymphoid neoplasms with defining gene rearrangement.</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":"142323385","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

11. Developing a robust bioinformatics workflow to support personalized neoantigen vaccine clinical trials 11.开发强大的生物信息学工作流程以支持个性化新抗原疫苗临床试验

IF 1.4 4区医学

Cancer Genetics Pub Date : 2024-08-01 DOI: 10.1016/j.cancergen.2024.08.013

{"title":"11. Developing a robust bioinformatics workflow to support personalized neoantigen vaccine clinical trials","authors":"","doi":"10.1016/j.cancergen.2024.08.013","DOIUrl":"10.1016/j.cancergen.2024.08.013","url":null,"abstract":"<div><div>Personalized cancer vaccines (PCVs) leverage immunogenomics strategies to combat cancer. Somatic mutations in tumor cells generate neoantigens that may get presented on the tumor cell's surface by MHC molecules. Immunotherapies target neoantigens to stimulate tumor-specific immune responses. Our bioinformatics workflow has designed vaccines for over 170 patients across 11 of the 180 neoantigen vaccine trials on clinicaltrials.gov.</div><div>Despite the rise in PCV-related interventions, gaps in established protocols addressing the complexities associated with the design of PCVs still remain. Here, we summarize our bioinformatics pipeline and describe measures taken to ensure robust support for clinical trials at Washington University. Our Google Cloud immunotherapy pipeline (open MIT license) to predict neoantigen epitopes is implemented in Workflow Definition Language and containerized using Docker to ensure portability and reliability. The pVACtools software suite (pvactools.org) that carries out neoantigen identification and prioritization, is developed and updated following industry best practices including version control (Git), formal code review, automated unit and integration tests, and benchmark tests. The final steps of the bioinformatics workflow generate files recording the analysis parameters and QC results tailored to the FDA's requests. Candidates generated by the pipeline are reviewed at an Immunogenomics Tumor Board using the pVACview tool. Prioritized candidates undergo a rigorous examination of data QC metrics, variant support at genomic and transcriptomic levels, MHC binding prediction algorithms, and HLA allele concordance between the clinical data and in-silico prediction tools. Finally, a long-peptide order form generated by the pipeline is sent to the vaccine manufacturer for synthesis.</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":"142323464","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

15. Clinical impact of in-house molecular testing for underserved cancer patients in southern Alabama 15.内部分子检测对阿拉巴马州南部服务不足的癌症患者的临床影响

IF 1.4 4区医学

Cancer Genetics Pub Date : 2024-08-01 DOI: 10.1016/j.cancergen.2024.08.017

{"title":"15. Clinical impact of in-house molecular testing for underserved cancer patients in southern Alabama","authors":"","doi":"10.1016/j.cancergen.2024.08.017","DOIUrl":"10.1016/j.cancergen.2024.08.017","url":null,"abstract":"<div><div>Molecular profiling is critical in identifying genomic mutations for targeted cancer therapy. This study assesses the outcome of in-house molecular testing at a healthcare organization that cares for underserved population in southern Alabama.</div><div>We assessed the clinical impact of in-house single-gene mutation assays for <em>BRAF</em> V600 for metastatic melanoma, microsatellite instability (MSI) for colorectal carcinoma, and quantitative <em>BCR::ABL1</em> p210 for chronic myelogenous leukemia. We determined test result turnaround time (TAT), and QNS and specimen rejection rate.</div><div>For <em>BRAF</em> V600 assay, there were 63 cases with 43 (68%) <em>BRAF</em> wild type, 20 (32%) <em>BRAF</em> mutant, 0 (0%) QNS and specimen rejection, and <24 hours TAT. For MSI assay, there were 100 cases with 91 (91%) MSI-Stable, 9 (9%) MSI-High, 0 (0%) QNS and specimen rejection, and <24 hours TAT. For quantitative p210 assay, there were 185 cases with 126 (68%) p210 detected, 59 (32%) p210 not detected, 10 (5.4%) cases were rejected due to pre-analytical errors, and <24 hours TAT. For <em>BRAF</em> and MSI assays, QNS and specimen rejection rate was 0% for in-house testing vs. 12.5% for send-out. For quantitative <em>BCR::ABL1</em> p210 assay, the rate was 5.4% for in-house testing vs. 20% for send-out. The TAT for all in-house assays was <24 hours vs. >7 days for send-outs.</div><div>In-house molecular testing has significant positive clinical impact. Faster TAT, cost effectiveness and better management of testing are major advantages of local testing that would enable broader access to precision therapy for underserved cancer patients.</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":"142323469","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

24. Methylation sequencing enhances interpretation of clonal hematopoiesis dynamics 24.甲基化测序增强了对克隆造血动态的解读

IF 1.4 4区医学

Cancer Genetics Pub Date : 2024-08-01 DOI: 10.1016/j.cancergen.2024.08.026

{"title":"24. Methylation sequencing enhances interpretation of clonal hematopoiesis dynamics","authors":"","doi":"10.1016/j.cancergen.2024.08.026","DOIUrl":"10.1016/j.cancergen.2024.08.026","url":null,"abstract":"<div><div>Somatic mutations in hematopoietic stem cells give rise to clonal hematopoiesis (CH), a pre-malignant state that precedes hematologic malignancy. In current clinical practice, CH clone size as quantified by the variant allele fraction (VAF) is serially monitored with DNA sequencing. Increases in VAF are often interpreted as portending progression to malignancy. CH leads to a myeloid bias and VAF measurements can be confounded by cell-type proportions, which also vary according to immune demands. We developed a targeted enzymatic DNA methylation sequencing assay that costs ∼$80/sample (including reagents, library preparation and sequencing) and captures ∼4 million CpGs and applied it to 91 samples from patients with CH. We used the resulting methylation data to infer cell-type proportions. We found that predicted cell-type proportions for lymphocytes and granulocytes correlated highly with complete blood cell counts (R^2 = 0.84 and p-value = 2.65 × 10^-14; R2 = 0.88 and p-value = 4.31 × 10^-16), but predictions for monocytes were much less correlated (R^2 = 0.26, p-value = 2.04 × 10^-3). Furthermore, we observed that as monocyte proportion increased, so did reported percent change in VAF. Correlation was highest for clones driven by mutations in <em>TET2</em>, which have been shown to have more extreme degrees of myeloid bias. This work raises concerns about current methods of monitoring CH based solely on VAF. Given the low cost, cell-type proportion prediction from DNA methylation is a feasible addition to CH assays. Our work suggests that cell-type proportions would provide vital context for accurate interpretation of VAF throughout hematologic malignancy progression and treatment.</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":"142323388","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

55. Advancing bladder carcinoma diagnosis: The innovative potential of the BCDx multi-omics approach 55.推进膀胱癌诊断：BCDx 多组学方法的创新潜力

IF 1.4 4区医学

Cancer Genetics Pub Date : 2024-08-01 DOI: 10.1016/j.cancergen.2024.08.057

{"title":"55. Advancing bladder carcinoma diagnosis: The innovative potential of the BCDx multi-omics approach","authors":"","doi":"10.1016/j.cancergen.2024.08.057","DOIUrl":"10.1016/j.cancergen.2024.08.057","url":null,"abstract":"<div><div>The use of multi-omic biomarkers in liquid biopsies is emerging as a promising method for enhancing disease detection accuracy. However, it faces significant challenges, such as the complexity of integrating and interpreting data from various omic layers, which is time-consuming, low-throughput, and costly. Additionally, there is currently no simple instrument capable of detecting all the omics simultaneously. Early Is Good (EIG) has developed the Multi-Omic Integration Platform (MIP) to tackle these challenges in early disease detection. MIP can detect DNA, RNA, and proteins simultaneously using a standard plate reader, employing localized surface plasmon resonance (LSPR) of gold nanoparticles to enhance the bioluminescence resonance energy transfer (BRET) readout signal.</div><div>The novel MIP assay technology is applied to early bladder cancer recurrence monitoring using a multi-omic biomarker panel that includes miRNA, mRNA, lncRNA, and proteins. Current methods for identifying bladder cancer (BC) involve cystoscopy and urinary cytology. Cystoscopy, with 97% sensitivity for high-grade tumors, is invasive, operator-dependent, and costly. It often misses small or carcinoma in situ tumors, which can progress to muscle-invasive bladder cancer (MIBC) in about half of the patients. It also causes side effects like dysuria (50%), hematuria (19%), and urinary tract infections (3%), leading to discomfort, anxiety, and embarrassment. Urinary cytology, with 80-90% sensitivity and 98-100% specificity for high-grade tumors, struggles with low sensitivity (4-31%) for low-grade tumors and has a higher rate of false positives. This highlights the need for innovative approaches like the MIP, which offers non-invasive, highly sensitive, and comprehensive detection capabilities, potentially transforming the clinical management of bladder cancer. MIP has shown 100% sensitivity and 100% NPV for bladder cancer recurrence monitoring by combining the multi-omic biomarkers.</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":"142322857","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

35. Integrated comprehensive genomic profiling of meningiomas: A single institutional study 35.脑膜瘤的综合全面基因组图谱分析：单一机构研究

IF 1.4 4区医学

Cancer Genetics Pub Date : 2024-08-01 DOI: 10.1016/j.cancergen.2024.08.037

{"title":"35. Integrated comprehensive genomic profiling of meningiomas: A single institutional study","authors":"","doi":"10.1016/j.cancergen.2024.08.037","DOIUrl":"10.1016/j.cancergen.2024.08.037","url":null,"abstract":"<div><div>Meningioma is the most common central nervous system tumor and understudied because of its benign nature. High-grade meningiomas often show poorer outcome and enriched with high-risk copy-number-aberrations (CNAs) including losses/segmental-losses of chromosomes 1p, 3p, 4p/q, 6p/q, 10p/q, 14q, 18p/q and 19p/q, CDKN2A/B homozygous-deletion (CDKN2A/B-homo) and TERT promoter-mutation (TERTp) detected by comprehensive genomic profiling (CGP) including SNP-microarray, next generation sequencing (NGS) and DNA-methylation. In this study, we performed CGP on a large series of meningioma.</div><div>We identified 122 (45.2%) cases with high-risk CNAs in 270 cases assessed, including 33 WHO-grade-I, 67 WHO-grade-II and 22 WHO-grade-III. Fifty-one (41.8%) cases had hypodiploidy characterized by losses of 22, 14, 10, X/Y, 6 and 8; Eighteen (14.8%) showed polyploidy with relative losses of 1p, 14, 18, 6 and 10. In 53 (43.4%) cases with near-diploidy, half showed complex CNAs with losses/segmental-losses involving 1p, 3p, 19p,14q and 6q. Five cases (4.1%) showed CDKN2A/B-homo. NGS performed in 30 cases revealed mutations in NF2 (n=20), ARID1A (n=7), MSH6 (n=4). Seven (6.6%, 7/106) had TERTp mutation. Methylation profiling matched classifier for meningioma in 92% (79/86) of cases tested. CGP upgraded 58% WHO-grade-I and 67.2% WHO-grade-II tumors to WHO-grade-II and III, respectively. Although follow-up data is limited, 51 patients (41.8%) had tumor recurrence.</div><div>Our study showed that meningiomas are enriched by high-risk CNAs even in low-grade tumors, less frequent TERTp mutation or CDKN2A/B-homo. CGP is of clinical importance for tumor molecular characterizations. CGP should be utilized clinically and integrated in future WHO classifications for tumor grading and risk stratification.</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":"142323289","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

12. Contextualizing clinical significance using FDA label supplemented DGI data 12.利用 FDA 标签补充 DGI 数据确定临床意义的内涵

IF 1.4 4区医学

Cancer Genetics Pub Date : 2024-08-01 DOI: 10.1016/j.cancergen.2024.08.014

{"title":"12. Contextualizing clinical significance using FDA label supplemented DGI data","authors":"","doi":"10.1016/j.cancergen.2024.08.014","DOIUrl":"10.1016/j.cancergen.2024.08.014","url":null,"abstract":"<div><div>The drug-gene interaction database (DGIdb) is a resource that aggregates interaction data from over 40 different resources into one platform with the primary goal of making the druggable genome accessible to clinicians and researchers. By providing a public, computationally accessible database, the DGIdb enables therapeutic insights through broad aggregation of DGI data.</div><div>As part of our aggregation process, DGIdb preserves data regarding interaction types, directionality, and other attributes that enable filtering or biochemical insight. However, source data are often incomplete and may not contain the original physiological context of the interaction. Without this context, the therapeutic relevance of an interaction may be compromised or lost. In this report, we address these missing data and extract therapeutic context from free-text sources. We apply existing large language models (LLMs) that have been fine-tuned on additional medical corpuses to tag and extract indications, cancer types, and relevant pharmacogenomics from free-text, FDA approved labels. We are then able to utilize our in-house normalization services to link extracted data back to formally grouped concepts.</div><div>In a preliminary test set of 355 FDA labels, we were able to normalize 59.4%, 49.8%, and 49.1% of extracted chemical, disease, and genetic entities back to harmonized concepts. Extracting this data allows us to supplement our existing interactions with relevant context that may inform the therapeutic relevance of a particular interaction. Inclusion of these data will be particularly invaluable for variant interpretation pipelines where mutational status can lead to the identification of a lifesaving therapeutic and a positive patient outcome.</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":"142323465","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