Gene Mutational Clusters in the Tumors of Colorectal Cancer Patients With a Family History of Cancer
IntroductionFamily history is a high-risk factor for colorectal cancer (CRC). The risk comes not only from known germline mutations but also from the other family-related mechanisms. Uncovering them would be an important step to improve the diagnosis and treatment of these patients.MethodSamples fro...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.814397/full |
| _version_ | 1811236449792557056 |
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| author | He Huang Ting Deng Yuntong Guo Hao Chen Xiaolong Cui Jingjing Duan Yuchong Yang Zhixin Guo Yi Ba |
| author_facet | He Huang Ting Deng Yuntong Guo Hao Chen Xiaolong Cui Jingjing Duan Yuchong Yang Zhixin Guo Yi Ba |
| author_sort | He Huang |
| collection | DOAJ |
| description | IntroductionFamily history is a high-risk factor for colorectal cancer (CRC). The risk comes not only from known germline mutations but also from the other family-related mechanisms. Uncovering them would be an important step to improve the diagnosis and treatment of these patients.MethodSamples from 168 patients with advanced CRC were collected and applied to next-generation sequencing of 624 pan-cancer genes. Genomic mutations and significantly mutated genes were identified. Significantly mutated genes and co-mutated genes were used to cluster patients. For each cluster of patients, mutational signatures were extracted. The identified mutational signatures were further validated in the other independent cohort.ResultSignificantly mutated genes including TP53, APC, KRAS, and SMAD4 were found associated with tumor mutational burden and microsatellite instability. LRP1, ACVR2A, and SETBP1 were found co-mutated. Patients with mutations in LRP1, ACVR2A, and SETBP1 tend to have a family history of cancer. Those patients tended to have right-sided tumors with high tumor mutational burden and microsatellite instability. Among them, signature analysis identified two possible etiologies, SBS10a (defective polymerase epsilon exonuclease domain) and SBS6 (defective DNA mismatch repair and microsatellite unstable tumors). These signatures were also found in another independent cohort.ConclusionThe gene cluster (LRP1, ACVR2A, and SETBP1) could be a good biomarker of these patients with a family risk, which was characterized by right-sidedness, high tumor mutational burden, and high microsatellite instability. |
| first_indexed | 2024-04-12T12:08:58Z |
| format | Article |
| id | doaj.art-5424a4b256a14d22bdd3fb861e7c41db |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-12T12:08:58Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-5424a4b256a14d22bdd3fb861e7c41db2022-12-22T03:33:38ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-06-011210.3389/fonc.2022.814397814397Gene Mutational Clusters in the Tumors of Colorectal Cancer Patients With a Family History of CancerHe Huang0Ting Deng1Yuntong Guo2Hao Chen3Xiaolong Cui4Jingjing Duan5Yuchong Yang6Zhixin Guo7Yi Ba8Department of Gastrointestinal Surgery, The First Hospital of Shanxi Medical University, Taiyuan, ChinaTianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, ChinaDepartment of Gastrointestinal Surgery, The First Hospital of Shanxi Medical University, Taiyuan, ChinaDepartment of Gastrointestinal Surgery, The First Hospital of Shanxi Medical University, Taiyuan, ChinaDepartment of Gastrointestinal Surgery, The First Hospital of Shanxi Medical University, Taiyuan, ChinaTianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, ChinaTianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, ChinaGastrointestinal Surgery, Hebei Dingzhou People’s Hospital, Dingzhou, ChinaTianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, ChinaIntroductionFamily history is a high-risk factor for colorectal cancer (CRC). The risk comes not only from known germline mutations but also from the other family-related mechanisms. Uncovering them would be an important step to improve the diagnosis and treatment of these patients.MethodSamples from 168 patients with advanced CRC were collected and applied to next-generation sequencing of 624 pan-cancer genes. Genomic mutations and significantly mutated genes were identified. Significantly mutated genes and co-mutated genes were used to cluster patients. For each cluster of patients, mutational signatures were extracted. The identified mutational signatures were further validated in the other independent cohort.ResultSignificantly mutated genes including TP53, APC, KRAS, and SMAD4 were found associated with tumor mutational burden and microsatellite instability. LRP1, ACVR2A, and SETBP1 were found co-mutated. Patients with mutations in LRP1, ACVR2A, and SETBP1 tend to have a family history of cancer. Those patients tended to have right-sided tumors with high tumor mutational burden and microsatellite instability. Among them, signature analysis identified two possible etiologies, SBS10a (defective polymerase epsilon exonuclease domain) and SBS6 (defective DNA mismatch repair and microsatellite unstable tumors). These signatures were also found in another independent cohort.ConclusionThe gene cluster (LRP1, ACVR2A, and SETBP1) could be a good biomarker of these patients with a family risk, which was characterized by right-sidedness, high tumor mutational burden, and high microsatellite instability.https://www.frontiersin.org/articles/10.3389/fonc.2022.814397/fullcolorectal cancermutationfamily historyco-mutationbiomarkers |
| spellingShingle | He Huang Ting Deng Yuntong Guo Hao Chen Xiaolong Cui Jingjing Duan Yuchong Yang Zhixin Guo Yi Ba Gene Mutational Clusters in the Tumors of Colorectal Cancer Patients With a Family History of Cancer Frontiers in Oncology colorectal cancer mutation family history co-mutation biomarkers |
| title | Gene Mutational Clusters in the Tumors of Colorectal Cancer Patients With a Family History of Cancer |
| title_full | Gene Mutational Clusters in the Tumors of Colorectal Cancer Patients With a Family History of Cancer |
| title_fullStr | Gene Mutational Clusters in the Tumors of Colorectal Cancer Patients With a Family History of Cancer |
| title_full_unstemmed | Gene Mutational Clusters in the Tumors of Colorectal Cancer Patients With a Family History of Cancer |
| title_short | Gene Mutational Clusters in the Tumors of Colorectal Cancer Patients With a Family History of Cancer |
| title_sort | gene mutational clusters in the tumors of colorectal cancer patients with a family history of cancer |
| topic | colorectal cancer mutation family history co-mutation biomarkers |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.814397/full |
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