Genomic Profiling of Small Intestine Cancers From a Real-World Data Set Identifies Subgroups With Actionable Alterations.

IF 5.3 2区医学 Q1 ONCOLOGY

JCO precision oncology Pub Date : 2024-08-01 DOI:10.1200/PO.23.00425

Hiroyuki Takeda, Hiroyuki Yamamoto, Ritsuko Oikawa, Kumiko Umemoto, Hiroyuki Arai, Takuro Mizukami, Kazuki Ogawa, Yoshiyasu Uchida, Yusuke Nagata, Yohei Kubota, Ayako Doi, Yoshiki Horie, Takashi Ogura, Naoki Izawa, Jay A Moore, Ethan S Sokol, Yu Sunakawa

{"title":"Genomic Profiling of Small Intestine Cancers From a Real-World Data Set Identifies Subgroups With Actionable Alterations.","authors":"Hiroyuki Takeda, Hiroyuki Yamamoto, Ritsuko Oikawa, Kumiko Umemoto, Hiroyuki Arai, Takuro Mizukami, Kazuki Ogawa, Yoshiyasu Uchida, Yusuke Nagata, Yohei Kubota, Ayako Doi, Yoshiki Horie, Takashi Ogura, Naoki Izawa, Jay A Moore, Ethan S Sokol, Yu Sunakawa","doi":"10.1200/PO.23.00425","DOIUrl":null,"url":null,"abstract":"Purpose: Panel-based comprehensive genomic profiling (CGP) is used in clinical practice worldwide; however, large real-world data (RWD) of patients with advanced small intestine cancer have not been characterized. We investigated differences in the prevalence of clinically relevant alterations across molecularly defined or age-stratified subgroups.Patients and methods: This was a collaborative biomarker study of RWD from CGP testing (Foundation Medicine, Inc). Hybrid capture was conducted on at least 324 cancer-related genes and select introns from up to 31 genes frequently rearranged in cancer. Overall, 1,364 patients with advanced small intestine cancer were available for analyses and were stratified by age (≥40 years/<40 years), microsatellite instability (MSI) status, tumor mutational burden (TMB) status (high ≥10/low <10 Muts/Mb), and select gene alterations. The frequency of alterations was analyzed using a chi-square test with Yate's correction.Results: Genes with frequent alterations included TP53 (59.8%), KRAS (54.8%), APC (27.7%), and CDKN2A (22.4%). Frequent genes with amplifications were MYC (6.7%), MDM2 (5.9%), GATA6 (5.5%), and CCND1 (3.4%). Patients younger than 40 years had significantly lower frequency of APC mutations than those 40 years and older (10.4% v 28.7%; P = .0008). Druggable genomic alterations were detected in 22.3% of patients: BRAF V600E (1.2%), BRCA1 (1.8%), BRCA2 (3.2%), ERBB2 amplification (3.2%), KRAS G12C (3.3%), NTRK1/2/3 fusion (0.07%), MSI-high (7.0%), and TMB-high (12.2%), with no significant differences in the frequency according to age (<40 years v ≥40 years; 22.1% v 22.3%). TMB of 10-20 Mut/Mb was observed in 4.8% of patients, and TMB ≥20 Mut/Mb was seen in 7.3% of the cohort.Conclusion: RWD from clinical panel testing revealed the genomic landscape in small intestine cancer by subgroup. These findings provide insights for the future development of treatments in advanced small intestine cancer.","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"8 ","pages":"e2300425"},"PeriodicalIF":5.3000,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"JCO precision oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1200/PO.23.00425","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Purpose: Panel-based comprehensive genomic profiling (CGP) is used in clinical practice worldwide; however, large real-world data (RWD) of patients with advanced small intestine cancer have not been characterized. We investigated differences in the prevalence of clinically relevant alterations across molecularly defined or age-stratified subgroups.

Patients and methods: This was a collaborative biomarker study of RWD from CGP testing (Foundation Medicine, Inc). Hybrid capture was conducted on at least 324 cancer-related genes and select introns from up to 31 genes frequently rearranged in cancer. Overall, 1,364 patients with advanced small intestine cancer were available for analyses and were stratified by age (≥40 years/<40 years), microsatellite instability (MSI) status, tumor mutational burden (TMB) status (high ≥10/low <10 Muts/Mb), and select gene alterations. The frequency of alterations was analyzed using a chi-square test with Yate's correction.

Results: Genes with frequent alterations included TP53 (59.8%), KRAS (54.8%), APC (27.7%), and CDKN2A (22.4%). Frequent genes with amplifications were MYC (6.7%), MDM2 (5.9%), GATA6 (5.5%), and CCND1 (3.4%). Patients younger than 40 years had significantly lower frequency of APC mutations than those 40 years and older (10.4% v 28.7%; P = .0008). Druggable genomic alterations were detected in 22.3% of patients: BRAF V600E (1.2%), BRCA1 (1.8%), BRCA2 (3.2%), ERBB2 amplification (3.2%), KRAS G12C (3.3%), NTRK1/2/3 fusion (0.07%), MSI-high (7.0%), and TMB-high (12.2%), with no significant differences in the frequency according to age (<40 years v ≥40 years; 22.1% v 22.3%). TMB of 10-20 Mut/Mb was observed in 4.8% of patients, and TMB ≥20 Mut/Mb was seen in 7.3% of the cohort.

Conclusion: RWD from clinical panel testing revealed the genomic landscape in small intestine cancer by subgroup. These findings provide insights for the future development of treatments in advanced small intestine cancer.

查看原文本刊更多论文

从真实世界数据集中对小肠癌进行基因组剖析，发现具有可操作改变的亚组。

目的：基于小组的综合基因组图谱分析（CGP）已在全球范围内用于临床实践；然而，晚期小肠癌患者的大量真实世界数据（RWD）尚未被描述。我们研究了不同分子定义或年龄分层亚组中临床相关改变发生率的差异：这是一项通过 CGP 检测（Foundation Medicine, Inc）对 RWD 进行的生物标记物合作研究。对至少 324 个癌症相关基因和多达 31 个在癌症中经常发生重排的基因的部分内含子进行了混合捕获。共有 1,364 名晚期小肠癌患者可供分析，并按年龄（≥40 岁/结果）进行了分层：经常发生改变的基因包括 TP53（59.8%）、KRAS（54.8%）、APC（27.7%）和 CDKN2A（22.4%）。常见的扩增基因包括MYC（6.7%）、MDM2（5.9%）、GATA6（5.5%）和CCND1（3.4%）。40 岁以下患者的 APC 突变频率明显低于 40 岁及以上患者（10.4% 对 28.7%；P = 0.0008）。22.3%的患者检测到可用药的基因组改变：22.3% 的患者检测到了可用药的基因组改变：BRAF V600E (1.2%)、BRCA1 (1.8%)、BRCA2 (3.2%)、ERBB2 扩增 (3.2%)、KRAS G12C (3.3%)、NTRK1/2/3 融合 (0.07%)、MSI-高 (7.0%) 和 TMB-高 (12.2%)。4.8%的患者的TMB为10-20 Mut/Mb，7.3%的患者的TMB≥20 Mut/Mb：临床面板检测的RWD揭示了小肠癌各亚组的基因组状况。这些发现为未来开发晚期小肠癌的治疗方法提供了启示。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

JCO precision oncology ONCOLOGY-

CiteScore

9.10

自引率

4.30%

发文量

363