Genomic landscape of pathogenic mutations in Pakistani population with late-stage colorectal cancer.

IF 1.2 4区医学 Q2 MEDICINE, GENERAL & INTERNAL

Pakistan Journal of Medical Sciences Pub Date : 2025-05-01 DOI:10.12669/pjms.41.5.10265

Zeeshan Ansar, Asghar Nasir, Tariq Moatter, Uzma Shamsi

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引用次数: 0

Abstract

Objective: To assess the frequencies of pathogenic mutations in Pakistani population with late-stage Colorectal cancer (CRC).

Methods: This was a descriptive analysis of CRC patients who got their next-generation sequencing (NGS) tests (targeted panel) done at AKUH, Karachi between January 2021 and December 2021. Pathogenic variants were identified using American College of Medical Genetics and Genomics (ACMG) classification.

Results: Among the 35 CRC patients analyzed, 31.4% were < 50 years old and 60% were males. Mutation analysis showed a high prevalence of TP53 mutations in 23 patients (65.7%). KRAS mutations were detected in 19 patients (54.3%) Other mutations included PIK3CA in 3(8.6%), NRAS in 3(8.6%), EGFR in 3(8.6%), and MET in 1(2.9%). Double gene mutation (KRAS and TP53) were observed in 13 (37.1%) and (PIK3CA and KRAS) in 2 (5.71%) samples. A triple gene mutations (KRAS, TP53, and PIK3CA) were found in 1 (3%) of CRC tumors. The remaining samples were wild type for genes analyzed. Microsatellite instability (MSI) status was assessed, revealing 2.9% MSI-high tumors, 37.1% MSI-stable tumors, and a concerningly high proportion (60.0%) of samples where MSI testing was not performed.

Conclusion: This study highlights distinct a genetic profile of CRC in the Pakistani population, characterized by a significant prevalence of TP53 and KRAS mutations.

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巴基斯坦晚期结直肠癌人群致病性突变的基因组图谱。

目的：了解巴基斯坦晚期结直肠癌（CRC）人群致病性突变的频率。方法：这是对2021年1月至2021年12月在卡拉奇AKUH进行下一代测序（NGS）测试（靶向小组）的结直肠癌患者的描述性分析。采用美国医学遗传与基因组学学院（ACMG）分类鉴定致病变异。结果：35例结直肠癌患者中，年龄< 50岁的占31.4%，男性占60%。突变分析显示23例患者（65.7%）TP53突变高发。KRAS突变19例（54.3%），其他突变包括PIK3CA 3例（8.6%），NRAS 3例（8.6%），EGFR 3例（8.6%），MET 1例（2.9%）。KRAS和TP53双基因突变13例（37.1%），PIK3CA和KRAS双基因突变2例（5.71%）。三基因突变（KRAS， TP53和PIK3CA）在1（3%）的结直肠癌肿瘤中被发现。剩余样本为野生型。对微卫星不稳定性（MSI）状态进行评估，发现2.9%的MSI高肿瘤，37.1%的MSI稳定肿瘤，以及未进行MSI检测的高比例（60.0%）样本。结论：本研究强调了巴基斯坦人群中CRC的独特遗传谱，其特征是TP53和KRAS突变的显著流行。

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

Pakistan Journal of Medical Sciences 医学-医学：内科

CiteScore

4.10

自引率

9.10%

发文量

363

审稿时长

3-6 weeks

期刊介绍： It is a peer reviewed medical journal published regularly since 1984. It was previously known as quarterly "SPECIALIST" till December 31st 1999. It publishes original research articles, review articles, current practices, short communications & case reports. It attracts manuscripts not only from within Pakistan but also from over fifty countries from abroad. Copies of PJMS are sent to all the import medical libraries all over Pakistan and overseas particularly in South East Asia and Asia Pacific besides WHO EMRO Region countries. Eminent members of the medical profession at home and abroad regularly contribute their write-ups, manuscripts in our publications. We pursue an independent editorial policy, which allows an opportunity to the healthcare professionals to express their views without any fear or favour. That is why many opinion makers among the medical and pharmaceutical profession use this publication to communicate their viewpoint.