Clinical actionability of Comprehensive Genomic Profiling in India

IF 1 Q4 GENETICS & HEREDITY

Gene Reports Pub Date : 2025-04-11 DOI:10.1016/j.genrep.2025.102222

Prasanth S. Ariyannur , Reenu Anne Joy , Rahul Ramachandran, Thelakkattusserry Kamalasanan Sukrishna, Ajit Nambiar , Rajasekhar Kommu, Moni Abraham Kuriakose, Venkataramanan Ramachandran, Prashant Kumar

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Abstract

The validation and clinical utility of Comprehensive Genomic Profiling (CGP) for identifying somatic genomic mutations have been challenging within the Indian Oncology practice. The primary obstacles to establishing clinical utility are cost, availability, lack of expertise in testing, adoptability and implementation of therapeutic recommendations. However, the absence of standardized laboratory methods in Indian cases has not been previously addressed. We validated a widely applied CGP assay, TruSight Oncology 500, in a reference laboratory. Subsequently, the clinical utility in a series of 192 cases comprising late-stage tumor specimens from common solid cancer types was examined. The identified somatic variants were classified based on the AMP Tier classification to determine their clinical utility. Lung adenocarcinoma was the most common, followed by breast and gastrointestinal cancers. The most common genes with mutations were TP53 (36.5 %), MYC (29.7 %), EGFR (20.8 %), KRAS (16 %), PIK3CA (20.6 %), BRAF (11 %), and ERBB2 (10 %). Therapeutic recommendations based on AMP Guidelines Tier 1A were found in 33 % of cases, Tier 1B in 49 %, and Tier IIC in 83 % of cases. TMB-high (>10muts/Mb) in 21.5 % of cases, TMB-Low (≤9 muts/Mb) in 77.6 % of cases, MSI-L (1–30 %) was identified in 85.4 % of cases, and MSS (<1 %) in 14 % of cases. Overall, we identified therapeutically actionable mutations in 83 % of cases of solid tumors that had undergone CGP.

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综合基因组图谱在印度的临床可操作性

综合基因组图谱（CGP）用于鉴定体细胞基因组突变的验证和临床应用在印度肿瘤学实践中一直具有挑战性。建立临床效用的主要障碍是成本、可获得性、缺乏检测方面的专业知识、可接受性和治疗建议的实施。然而，在印度病例中缺乏标准化的实验室方法以前没有得到解决。我们在参比实验室验证了一种广泛应用的CGP检测，TruSight Oncology 500。随后，对192例包括常见实体癌类型晚期肿瘤标本的临床应用进行了研究。根据AMP分级对鉴定的体细胞变异进行分类，以确定其临床效用。肺腺癌是最常见的，其次是乳腺癌和胃肠道癌。最常见的突变基因是TP53（36.5%）、MYC（29.7%）、EGFR（20.8%）、KRAS（16%）、PIK3CA（20.6%）、BRAF（11%）和ERBB2（10%）。33%的病例发现基于AMP指南的1A级治疗建议，49%的病例发现1B级治疗建议，83%的病例发现IIC级治疗建议。tmb -高（10muts/Mb）的病例占21.5%，tmb -低（≤9 muts/Mb）的病例占77.6%,MSI-L（1 - 30%）的病例占85.4%，MSS（1%）的病例占14%。总的来说，我们在83%接受过CGP的实体瘤病例中发现了可治疗的突变。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Gene Reports Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

3.30

自引率

7.70%

发文量

246

审稿时长

49 days

期刊介绍： Gene Reports publishes papers that focus on the regulation, expression, function and evolution of genes in all biological contexts, including all prokaryotic and eukaryotic organisms, as well as viruses. Gene Reports strives to be a very diverse journal and topics in all fields will be considered for publication. Although not limited to the following, some general topics include: DNA Organization, Replication & Evolution -Focus on genomic DNA (chromosomal organization, comparative genomics, DNA replication, DNA repair, mobile DNA, mitochondrial DNA, chloroplast DNA). Expression & Function - Focus on functional RNAs (microRNAs, tRNAs, rRNAs, mRNA splicing, alternative polyadenylation) Regulation - Focus on processes that mediate gene-read out (epigenetics, chromatin, histone code, transcription, translation, protein degradation). Cell Signaling - Focus on mechanisms that control information flow into the nucleus to control gene expression (kinase and phosphatase pathways controlled by extra-cellular ligands, Wnt, Notch, TGFbeta/BMPs, FGFs, IGFs etc.) Profiling of gene expression and genetic variation - Focus on high throughput approaches (e.g., DeepSeq, ChIP-Seq, Affymetrix microarrays, proteomics) that define gene regulatory circuitry, molecular pathways and protein/protein networks. Genetics - Focus on development in model organisms (e.g., mouse, frog, fruit fly, worm), human genetic variation, population genetics, as well as agricultural and veterinary genetics. Molecular Pathology & Regenerative Medicine - Focus on the deregulation of molecular processes in human diseases and mechanisms supporting regeneration of tissues through pluripotent or multipotent stem cells.