来自撒哈拉以南非洲的年轻结直肠癌患者的体细胞全外显子组测序揭示了新的见解。

IF 3.7 2区 医学 Q1 PATHOLOGY
Alessandro Pietro Aldera, Dennis Owusu, Leonardo Biral, Komala Pillay, Adam Boutall, Sandeep Dave, Raj Ramesar
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引用次数: 0

摘要

结直肠癌(CRC)是撒哈拉以南非洲地区发病率和死亡率的常见原因。早发、微卫星稳定型(MSS) CRC的发病率正在上升,而这些病变的肿瘤生物学分类很差。来自尼日利亚一个研究中心的初步数据发现,驱动基因的突变频率和信号通路的改变存在差异。我们试图通过全外显子组测序来研究潜在的替代驱动基因和信号通路。83例通过质量控制筛选纳入分析(77例MSS, 4例微卫星不稳定性高,2例POLE突变)。APC、TP53和KRAS是最常见的突变驱动基因,尽管频率低于预期。在我们的队列中没有BRAF V600E突变。虽然主要驱动基因的突变频率存在差异,但发现致癌途径改变的频率相似。FAT4(26%)和TET2(15%)是重要的突变驱动基因和潜在的治疗靶点,有待进一步研究。我们强调了来自撒哈拉以南非洲的年轻CRC队列中驱动基因突变的明显差异,并确定FAT4和TET2是更常见的潜在驱动因素,也是潜在的治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Somatic whole exome sequencing of colorectal carcinoma in young patients from sub-Saharan Africa reveals novel insights

Somatic whole exome sequencing of colorectal carcinoma in young patients from sub-Saharan Africa reveals novel insights

Somatic whole exome sequencing of colorectal carcinoma in young patients from sub-Saharan Africa reveals novel insights

Somatic whole exome sequencing of colorectal carcinoma in young patients from sub-Saharan Africa reveals novel insights

Colorectal carcinoma (CRC) is a frequent cause of morbidity and mortality in sub-Saharan Africa. The incidence of early-onset, microsatellite stable (MSS) CRC is on the rise, and the tumour biology of these lesions is poorly categorised. Preliminary data from one centre in Nigeria found differences in the frequencies of mutations in driver genes and altered signalling pathways. We sought to investigate potential alternative driver genes and signalling pathways by whole exome sequencing. Eighty-three cases passed quality control filters and were included in the analysis (77 MSS, 4 microsatellite instability-high, and 2 POLE mutant). APC, TP53, and KRAS were among the most frequently mutated driver genes, although at a lower frequency than expected. BRAF V600E mutations were absent in our cohort. Although there were differences in the frequencies of mutations in the major driver genes, the frequencies of oncogenic pathway alterations were found to be similar. FAT4 (26%) and TET2 (15%) emerged as important mutated driver genes and potential therapeutic targets for further investigation. We have highlighted distinct differences in driver gene mutations in our cohort of young CRC from sub-Saharan Africa and have identified FAT4 and TET2 as potential drivers that are more common and are potential therapeutic targets.

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来源期刊
Journal of Pathology Clinical Research
Journal of Pathology Clinical Research Medicine-Pathology and Forensic Medicine
CiteScore
7.40
自引率
2.40%
发文量
47
审稿时长
20 weeks
期刊介绍: The Journal of Pathology: Clinical Research and The Journal of Pathology serve as translational bridges between basic biomedical science and clinical medicine with particular emphasis on, but not restricted to, tissue based studies. The focus of The Journal of Pathology: Clinical Research is the publication of studies that illuminate the clinical relevance of research in the broad area of the study of disease. Appropriately powered and validated studies with novel diagnostic, prognostic and predictive significance, and biomarker discover and validation, will be welcomed. Studies with a predominantly mechanistic basis will be more appropriate for the companion Journal of Pathology.
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