Actionable Genes and Carcinogenic Pathways for Gastric Cancer in Latinos

IF 3.1 2区医学 Q2 ONCOLOGY

Cancer Medicine Pub Date : 2025-09-09 DOI:10.1002/cam4.71216

Ingrid M. Montes-Rodríguez, Hilmaris Centeno-Girona, Sol V. Pérez-Mártir, Noridza Rivera, Marcia Cruz-Correa

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Abstract

Background

Gastric cancer (GC) is the fourth leading cause of cancer-related death globally. Tumor profiling has revealed actionable gene alterations that guide treatment strategies and enhance survival. Among Hispanics living in Puerto Rico (PRH), GC ranks among the top 10 causes of cancer-related death. However, the genetic mutational landscape of GC tumors from PRH remains unexplored. This study aimed to identify the most prevalent genetic alterations in GC tumors among PRH.

Methods

We examined tumor mutational profiles of GC from 106 PRH between 2015 and 2022 (provided by CARIS Life Sciences and the Precision Oncology Alliance). Next-generation sequencing data were available for 85 cases, which were categorized as hypermutated (≥ 10 mutations/megabase) or non-hypermutated (< 10 mutations/megabase).

Results

Among the non-hypermutated cases, the most frequently mutated genes were TP53 (56.9%), CDH1 (29.2%), ARID1A (27.4%), and KMT2D (25.7%). Compared to TCGA, a majority non-Hispanic cohort, PRH had significantly higher mutational frequencies in driver genes in both intestinal type (TP53, CBLB, and MYH11) and diffuse type (CDH1, ARID1A, and KMT2D) GC.

Discussion

Intestinal-type GC in PR aligns with the chromosomal instability (CIN) molecular classification, showing a higher frequency of TP53 mutations than TCGA, potentially indicating more aggressive tumor biology and poorer prognosis. Diffuse-type GC showed higher CDH1 mutations, correlating with the genomically stable (GS) classification, characterized by fewer chromosomal changes but significant genetic alterations, including those in ARID1A and KMT2D.

Conclusions

This study shows that the unique genetic landscape of GC tumors in this group may lead to more aggressive cases and affect treatment responses, contributing to higher mortality rates. The higher mutation rates in biomarkers related to prognosis and therapy suggest that further research might uncover additional susceptibility variants. This underscores the importance of including Hispanics in genomic studies to better understand the genetic pathways associated with the risk and progression of GC.

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拉丁美洲人胃癌的可动基因和致癌途径

胃癌（GC）是全球第四大癌症相关死亡原因。肿瘤分析揭示了可操作的基因改变，指导治疗策略和提高生存率。在波多黎各（PRH）居住的西班牙裔人中，胃癌是癌症相关死亡的十大原因之一。然而，来自PRH的GC肿瘤的基因突变景观仍未被探索。本研究旨在确定PRH中GC肿瘤中最普遍的遗传改变。方法：研究了2015年至2022年间106例PRH的GC突变谱（由CARIS生命科学和精密肿瘤联盟提供）。85例患者可获得新一代测序数据，分为超突变（≥10个突变/兆基）和非超突变（<； 10个突变/兆基）。结果在非高突变病例中，最常见的突变基因为TP53（56.9%）、CDH1（29.2%）、ARID1A（27.4%）和KMT2D（25.7%）。与TCGA（大多数非西班牙裔队列）相比，PRH在肠型（TP53， CBLB和MYH11）和弥漫型（CDH1， ARID1A和KMT2D） GC中驱动基因的突变频率都明显更高。PR中的肠型GC与染色体不稳定性（CIN）分子分类一致，TP53突变频率高于TCGA，可能表明肿瘤生物学更具侵袭性，预后较差。弥散型GC表现出较高的CDH1突变，与基因组稳定（GS）分类相关，其特征是较少的染色体改变，但显著的遗传改变，包括ARID1A和KMT2D。结论该研究表明，该群体中GC肿瘤的独特遗传景观可能导致更具侵袭性的病例并影响治疗反应，从而导致更高的死亡率。与预后和治疗相关的生物标志物较高的突变率表明，进一步的研究可能会发现更多的易感性变异。这强调了将西班牙裔纳入基因组研究的重要性，以更好地了解与胃癌风险和进展相关的遗传途径。

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

Cancer Medicine ONCOLOGY-

CiteScore

5.50

自引率

2.50%

发文量

907

审稿时长

19 weeks

期刊介绍： Cancer Medicine is a peer-reviewed, open access, interdisciplinary journal providing rapid publication of research from global biomedical researchers across the cancer sciences. The journal will consider submissions from all oncologic specialties, including, but not limited to, the following areas: Clinical Cancer Research Translational research ∙ clinical trials ∙ chemotherapy ∙ radiation therapy ∙ surgical therapy ∙ clinical observations ∙ clinical guidelines ∙ genetic consultation ∙ ethical considerations Cancer Biology: Molecular biology ∙ cellular biology ∙ molecular genetics ∙ genomics ∙ immunology ∙ epigenetics ∙ metabolic studies ∙ proteomics ∙ cytopathology ∙ carcinogenesis ∙ drug discovery and delivery. Cancer Prevention: Behavioral science ∙ psychosocial studies ∙ screening ∙ nutrition ∙ epidemiology and prevention ∙ community outreach. Bioinformatics: Gene expressions profiles ∙ gene regulation networks ∙ genome bioinformatics ∙ pathwayanalysis ∙ prognostic biomarkers. Cancer Medicine publishes original research articles, systematic reviews, meta-analyses, and research methods papers, along with invited editorials and commentaries. Original research papers must report well-conducted research with conclusions supported by the data presented in the paper.