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
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oai:doaj.org-article:2c8e8e86d9754e66a2e676592b8c377c2021-12-02T10:54:01ZGermline Mutation Landscape and Associated Clinical Characteristics in Chinese Patients With Renal Cell Carcinoma2234-943X10.3389/fonc.2021.737547https://doaj.org/article/2c8e8e86d9754e66a2e676592b8c377c2021-12-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fonc.2021.737547/fullhttps://doaj.org/toc/2234-943XBackgroundRenal 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.Wen KongTongtong YangXiaodong WenZhongyi MuCheng ZhaoSujun HanJing TianXinhao ZhangTao ZhouYanrui ZhangFeng LouShanbo CaoHuina WangJin ZhangFrontiers Media S.A.articlerenal cell carcinomagermline mutationsChinese populationpathogenic variationsecond hit eventsNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENFrontiers in Oncology, Vol 11 (2021) |
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DOAJ |
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EN |
| topic |
renal cell carcinoma germline mutations Chinese population pathogenic variation second hit events Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 |
| spellingShingle |
renal cell carcinoma germline mutations Chinese population pathogenic variation second hit events Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 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 |
| 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. |
| format |
article |
| 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 |
| title |
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_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_sort |
germline mutation landscape and associated clinical characteristics in chinese patients with renal cell carcinoma |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/2c8e8e86d9754e66a2e676592b8c377c |
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