Alessandro Pietro Aldera, Dennis Owusu, Leonardo Biral, Komala Pillay, Adam Boutall, Sandeep Dave, Raj Ramesar
{"title":"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。","authors":"Alessandro Pietro Aldera, Dennis Owusu, Leonardo Biral, Komala Pillay, Adam Boutall, Sandeep Dave, Raj Ramesar","doi":"10.1002/2056-4538.70048","DOIUrl":null,"url":null,"abstract":"<p>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 <i>POLE</i> mutant). <i>APC</i>, <i>TP53</i>, and <i>KRAS</i> were among the most frequently mutated driver genes, although at a lower frequency than expected. <i>BRAF</i> 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. <i>FAT4</i> (26%) and <i>TET2</i> (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 <i>FAT4</i> and <i>TET2</i> as potential drivers that are more common and are potential therapeutic targets.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"11 5","pages":""},"PeriodicalIF":3.7000,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12441016/pdf/","citationCount":"0","resultStr":"{\"title\":\"Somatic whole exome sequencing of colorectal carcinoma in young patients from sub-Saharan Africa reveals novel insights\",\"authors\":\"Alessandro Pietro Aldera, Dennis Owusu, Leonardo Biral, Komala Pillay, Adam Boutall, Sandeep Dave, Raj Ramesar\",\"doi\":\"10.1002/2056-4538.70048\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>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 <i>POLE</i> mutant). <i>APC</i>, <i>TP53</i>, and <i>KRAS</i> were among the most frequently mutated driver genes, although at a lower frequency than expected. <i>BRAF</i> 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. <i>FAT4</i> (26%) and <i>TET2</i> (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 <i>FAT4</i> and <i>TET2</i> as potential drivers that are more common and are potential therapeutic targets.</p>\",\"PeriodicalId\":48612,\"journal\":{\"name\":\"Journal of Pathology Clinical Research\",\"volume\":\"11 5\",\"pages\":\"\"},\"PeriodicalIF\":3.7000,\"publicationDate\":\"2025-09-16\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12441016/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Pathology Clinical Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://pathsocjournals.onlinelibrary.wiley.com/doi/10.1002/2056-4538.70048\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PATHOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Pathology Clinical Research","FirstCategoryId":"3","ListUrlMain":"https://pathsocjournals.onlinelibrary.wiley.com/doi/10.1002/2056-4538.70048","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PATHOLOGY","Score":null,"Total":0}
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.
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.