Genomic characterization of patients with colorectal cancer.

IF 2.4 4区医学 Q3 ONCOLOGY

Hereditary Cancer in Clinical Practice Pub Date : 2025-09-26 DOI:10.1186/s13053-025-00322-x

Marwa Mahdouani, Drenushe Zhuri, Fulya Dusenkalkan, Hakan Gurkan, Sinem Yalcintepe

{"title":"Genomic characterization of patients with colorectal cancer.","authors":"Marwa Mahdouani, Drenushe Zhuri, Fulya Dusenkalkan, Hakan Gurkan, Sinem Yalcintepe","doi":"10.1186/s13053-025-00322-x","DOIUrl":null,"url":null,"abstract":"Background: Hereditary colorectal cancer (CRC) predisposition syndromes account for 5-10% of all diagnosed CRC cases. Lynch syndrome (LS), Familial Adenomatous Polyposis (FAP), and MUTYH-associated polyposis (MAP) are well-characterized hereditary syndromes known to contribute to colorectal cancer predisposition. However, other inherited genetic factors beyond these established conditions remain underexplored. Recent advancements in next-generation sequencing (NGS) have facilitated the identification of germline pathogenic variants (gPV) in cancer predisposition genes, enhancing diagnostic and management strategies for hereditary CRC syndromes. Using this technology, this study aimed to investigate the genetic causes of CRC in 23 Turkish patients belonging to 23 different families.Methods: Patients with a personal or familial history of colorectal cancer (CRC) or polyposis were selected from a cohort of 54 individuals examined between 2019 and 2022. Genetic testing was performed using the TruSight® Cancer and Qiaseq panels on the Illumina NextSeq next-generation sequencing (NGS) platform.Results: A total of 23 variants were identified, including 10 pathogenic or likely pathogenic variants, 5 of which were novel. These germline pathogenic/likely pathogenic variants were detected in the key genes MLH1, MSH6, PMS2, and APC, which are associated with LS and FAP. Variants were also found in other genes, including FANCC, CHEK2, ATM, and MUC16. Additionally, 13 variants of uncertain significance (VUS) were identified, 5 of which were novel. These VUS were detected in the genes MUTYH (linked to MAP), ATR, XRCC3, PALB2, ATM, SYNE1, RAD51D, NF1, ABRAXAS1, ERBB2, FGFR, and CHEK2, necessitating further investigation to determine their potential role in CRC predisposition.Conclusion: These findings highlight the utility of NGS in identifying germline variants linked to hereditary CRC syndromes and emphasize the need for functional studies to assess the pathogenicity of VUS.","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":"23 1","pages":"21"},"PeriodicalIF":2.4000,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12465344/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Hereditary Cancer in Clinical Practice","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s13053-025-00322-x","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"ONCOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background: Hereditary colorectal cancer (CRC) predisposition syndromes account for 5-10% of all diagnosed CRC cases. Lynch syndrome (LS), Familial Adenomatous Polyposis (FAP), and MUTYH-associated polyposis (MAP) are well-characterized hereditary syndromes known to contribute to colorectal cancer predisposition. However, other inherited genetic factors beyond these established conditions remain underexplored. Recent advancements in next-generation sequencing (NGS) have facilitated the identification of germline pathogenic variants (gPV) in cancer predisposition genes, enhancing diagnostic and management strategies for hereditary CRC syndromes. Using this technology, this study aimed to investigate the genetic causes of CRC in 23 Turkish patients belonging to 23 different families.

Methods: Patients with a personal or familial history of colorectal cancer (CRC) or polyposis were selected from a cohort of 54 individuals examined between 2019 and 2022. Genetic testing was performed using the TruSight^® Cancer and Qiaseq panels on the Illumina NextSeq next-generation sequencing (NGS) platform.

Results: A total of 23 variants were identified, including 10 pathogenic or likely pathogenic variants, 5 of which were novel. These germline pathogenic/likely pathogenic variants were detected in the key genes MLH1, MSH6, PMS2, and APC, which are associated with LS and FAP. Variants were also found in other genes, including FANCC, CHEK2, ATM, and MUC16. Additionally, 13 variants of uncertain significance (VUS) were identified, 5 of which were novel. These VUS were detected in the genes MUTYH (linked to MAP), ATR, XRCC3, PALB2, ATM, SYNE1, RAD51D, NF1, ABRAXAS1, ERBB2, FGFR, and CHEK2, necessitating further investigation to determine their potential role in CRC predisposition.

Conclusion: These findings highlight the utility of NGS in identifying germline variants linked to hereditary CRC syndromes and emphasize the need for functional studies to assess the pathogenicity of VUS.

查看原文本刊更多论文

结直肠癌患者的基因组特征。

背景：遗传性结直肠癌（CRC）易感综合征占所有诊断结直肠癌病例的5-10%。Lynch综合征（LS）、家族性腺瘤性息肉病（FAP）和mutyh相关息肉病（MAP）是已知的具有良好特征的遗传性综合征，可导致结直肠癌易感性。然而，除了这些既定条件外，其他遗传因素仍未得到充分探索。新一代测序（NGS）的最新进展促进了癌症易感基因种系致病变异（gPV）的鉴定，增强了遗传性CRC综合征的诊断和管理策略。利用这项技术，本研究旨在调查23名土耳其患者的CRC遗传原因，这些患者属于23个不同的家庭。方法：从2019年至2022年期间检查的54名个体中选择有个人或家族结直肠癌（CRC）或息肉病病史的患者。在Illumina NextSeq下一代测序（NGS）平台上使用TruSight®Cancer和Qiaseq面板进行基因检测。结果：共鉴定出23个变异，其中病原性或可能病原性变异10个，其中5个为新变异。在与LS和FAP相关的关键基因MLH1、MSH6、PMS2和APC中检测到这些种系致病/可能致病变异。在其他基因中也发现了变异，包括FANCC、CHEK2、ATM和MUC16。此外，还发现了13个不确定显著性变异（VUS），其中5个是新变异。这些VUS在MUTYH（与MAP相关）、ATR、XRCC3、PALB2、ATM、SYNE1、RAD51D、NF1、ABRAXAS1、ERBB2、FGFR和CHEK2基因中检测到，需要进一步研究以确定它们在结直肠癌易感性中的潜在作用。结论：这些发现强调了NGS在鉴定与遗传性CRC综合征相关的种系变异方面的效用，并强调了功能研究以评估VUS致病性的必要性。

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

Hereditary Cancer in Clinical Practice 医学-肿瘤学

CiteScore

3.10

自引率

5.90%

发文量

审稿时长

>12 weeks

期刊介绍： Hereditary Cancer in Clinical Practice is an open access journal that publishes articles of interest for the cancer genetics community and serves as a discussion forum for the development appropriate healthcare strategies. Cancer genetics encompasses a wide variety of disciplines and knowledge in the field is rapidly growing, especially as the amount of information linking genetic differences to inherited cancer predispositions continues expanding. With the increased knowledge of genetic variability and how this relates to cancer risk there is a growing demand not only to disseminate this information into clinical practice but also to enable competent debate concerning how such information is managed and what it implies for patient care. Topics covered by the journal include but are not limited to: Original research articles on any aspect of inherited predispositions to cancer. Reviews of inherited cancer predispositions. Application of molecular and cytogenetic analysis to clinical decision making. Clinical aspects of the management of hereditary cancers. Genetic counselling issues associated with cancer genetics. The role of registries in improving health care of patients with an inherited predisposition to cancer.