Germline Mutation Landscape and Associated Clinical Characteristics in Chinese Patients With Renal Cell Carcinoma
BackgroundRenal cell carcinoma (RCC) is a disease of genomic alterations, of which the complete panorama helps in facilitating molecular-guided therapy. Germline mutation profiles and associated somatic and clinical characteristics remains unexplored in Chinese RCC patients.MethodsWe retrospectively...
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Frontiers Media S.A.
2021-12-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2021.737547/full |
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| author | Wen Kong Tongtong Yang Xiaodong Wen Zhongyi Mu Cheng Zhao Sujun Han Jing Tian Xinhao Zhang Tao Zhou Yanrui Zhang Feng Lou Shanbo Cao Huina Wang Jin Zhang |
| author_facet | Wen Kong Tongtong Yang Xiaodong Wen Zhongyi Mu Cheng Zhao Sujun Han Jing Tian Xinhao Zhang Tao Zhou Yanrui Zhang Feng Lou Shanbo Cao Huina Wang Jin Zhang |
| author_sort | Wen Kong |
| collection | DOAJ |
| description | BackgroundRenal cell carcinoma (RCC) is a disease of genomic alterations, of which the complete panorama helps in facilitating molecular-guided therapy. Germline mutation profiles and associated somatic and clinical characteristics remains unexplored in Chinese RCC patients.MethodsWe retrospectively profiled the germline and somatic mutations of 322 unselected RCC patients using a panel consisting of 808 cancer-related genes. We categorized patients into three groups based on germline mutation status and compared the somatic mutation spectrum among different groups.ResultsApproximately one out of ten (9.9%) RCC patients were identified to carry pathogenic/likely pathogenic (P/LP) germline variants (PGVs), of which 3.7% were variants in syndromic RCC-associated genes and 6.2% were other cancer-predisposition genes. The most common PGV was found in VHL (2.2%), followed by FH, TSC2, ATM, BRCA1, NBN, and BLM (0.6% each). Young patients (≤46 years) were more likely to harbor PGVs. Variants in syndromic RCC-associated genes were predominant identified in young patients, while variants in other cancer-predisposition genes were found in patients >46 years more frequently. Furthermore, 39.3% (11/28) of patients carrying PGVs were detected to have somatic “second hit” events. Germline and somatic sequencing, including microsatellite instability (MSI) status analysis, provided potentially actionable therapeutic targets in 17.1% of patients in the whole cohort.ConclusionsOur results revealed that approximately 10% of RCC patients carried clinically significant germline mutations. Current guidelines recommendation for genetic testing seemed not sensitive enough to identify patients with hereditary RCC susceptibility. It is rational to promote genetic testing in RCC population. |
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| series | Frontiers in Oncology |
| spelling | doaj.art-2c8e8e86d9754e66a2e676592b8c377c2022-12-21T19:21:15ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-12-011110.3389/fonc.2021.737547737547Germline Mutation Landscape and Associated Clinical Characteristics in Chinese Patients With Renal Cell CarcinomaWen Kong0Tongtong Yang1Xiaodong Wen2Zhongyi Mu3Cheng Zhao4Sujun Han5Jing Tian6Xinhao Zhang7Tao Zhou8Yanrui Zhang9Feng Lou10Shanbo Cao11Huina Wang12Jin Zhang13Department of Urology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Translational Medicine, Acornmed Biotechnology Co., Ltd, Tianjin, ChinaDepartment of Urology, Shanxi Provincial People’s Hospital, Taiyuan, ChinaDepartment of Urology, Liaoning Cancer Hospital, Shenyang, ChinaDepartment of Urology, Xiangya Hospital of Central South University, Changsha, ChinaDepartment of Urology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Urology, The 2nd Hospital of Tianjin Medical University, Tianjin, ChinaDepartment of Translational Medicine, Acornmed Biotechnology Co., Ltd, Tianjin, ChinaDepartment of Translational Medicine, Acornmed Biotechnology Co., Ltd, Tianjin, ChinaDepartment of Translational Medicine, Acornmed Biotechnology Co., Ltd, Tianjin, ChinaDepartment of Translational Medicine, Acornmed Biotechnology Co., Ltd, Tianjin, ChinaDepartment of Translational Medicine, Acornmed Biotechnology Co., Ltd, Tianjin, ChinaDepartment of Translational Medicine, Acornmed Biotechnology Co., Ltd, Tianjin, ChinaDepartment of Urology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaBackgroundRenal cell carcinoma (RCC) is a disease of genomic alterations, of which the complete panorama helps in facilitating molecular-guided therapy. Germline mutation profiles and associated somatic and clinical characteristics remains unexplored in Chinese RCC patients.MethodsWe retrospectively profiled the germline and somatic mutations of 322 unselected RCC patients using a panel consisting of 808 cancer-related genes. We categorized patients into three groups based on germline mutation status and compared the somatic mutation spectrum among different groups.ResultsApproximately one out of ten (9.9%) RCC patients were identified to carry pathogenic/likely pathogenic (P/LP) germline variants (PGVs), of which 3.7% were variants in syndromic RCC-associated genes and 6.2% were other cancer-predisposition genes. The most common PGV was found in VHL (2.2%), followed by FH, TSC2, ATM, BRCA1, NBN, and BLM (0.6% each). Young patients (≤46 years) were more likely to harbor PGVs. Variants in syndromic RCC-associated genes were predominant identified in young patients, while variants in other cancer-predisposition genes were found in patients >46 years more frequently. Furthermore, 39.3% (11/28) of patients carrying PGVs were detected to have somatic “second hit” events. Germline and somatic sequencing, including microsatellite instability (MSI) status analysis, provided potentially actionable therapeutic targets in 17.1% of patients in the whole cohort.ConclusionsOur results revealed that approximately 10% of RCC patients carried clinically significant germline mutations. Current guidelines recommendation for genetic testing seemed not sensitive enough to identify patients with hereditary RCC susceptibility. It is rational to promote genetic testing in RCC population.https://www.frontiersin.org/articles/10.3389/fonc.2021.737547/fullrenal cell carcinomagermline mutationsChinese populationpathogenic variationsecond hit events |
| spellingShingle | Wen Kong Tongtong Yang Xiaodong Wen Zhongyi Mu Cheng Zhao Sujun Han Jing Tian Xinhao Zhang Tao Zhou Yanrui Zhang Feng Lou Shanbo Cao Huina Wang Jin Zhang Germline Mutation Landscape and Associated Clinical Characteristics in Chinese Patients With Renal Cell Carcinoma Frontiers in Oncology renal cell carcinoma germline mutations Chinese population pathogenic variation second hit events |
| title | Germline Mutation Landscape and Associated Clinical Characteristics in Chinese Patients With Renal Cell Carcinoma |
| title_full | Germline Mutation Landscape and Associated Clinical Characteristics in Chinese Patients With Renal Cell Carcinoma |
| title_fullStr | Germline Mutation Landscape and Associated Clinical Characteristics in Chinese Patients With Renal Cell Carcinoma |
| title_full_unstemmed | Germline Mutation Landscape and Associated Clinical Characteristics in Chinese Patients With Renal Cell Carcinoma |
| title_short | Germline Mutation Landscape and Associated Clinical Characteristics in Chinese Patients With Renal Cell Carcinoma |
| title_sort | germline mutation landscape and associated clinical characteristics in chinese patients with renal cell carcinoma |
| topic | renal cell carcinoma germline mutations Chinese population pathogenic variation second hit events |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2021.737547/full |
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