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Updated: May 25, 2025
Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
Germline Mutations in Renal Neoplasms and Their Clinicopathological Correlations
Meihua Chen1, Yang Liu2, Xianwei Yang2
1Department of Pathology, Shenzhen Bao'an District Traditional Chinese Medicine Hospital, Shenzhen, China.
Abstract:
Introduction. Germline mutations have been described in multiple renal neoplasm entities in the fifth edition of the World Health Organization Classification of Urinary and Male Genital Systems. However, our knowledge of renal neoplasms with germline mutations remains limited. Methods. To expand our understanding, 15 tumors with germline mutations were retrieved from 284 renal neoplasms that underwent next-generation sequencing, including well-known VHL, FH, SDHB, FLCN, TSC1, and less common genes such as MUTYH, NF2, and BARD1. Results. Interesting findings included clear cell renal cell carcinoma (RCC) with FH germline mutation and succinate dehydrogenase (SDH)-deficient RCC with high-grade transformation. Patients with germline mutations of these uncommon altered genes in renal neoplasms, such as MUTYH, NF2, and BARD1 were diagnosed with different renal entities, including entities with favorable outcomes (renal cell carcinoma with fibromyomatous stroma) or adverse outcomes (collecting duct carcinoma and FH deficient renal cell carcinoma). Conclusions. Besides the well-known germline mutations in renal neoplasms, we described germline mutations in some genes that are common in other sites but uncommon in the kidney. Although they cannot be used to determine a definite renal entity, they may also contribute to the pathogenesis of renal neoplasms. Tumors need to be diagnosed based on morphology, immunohistochemistry, and other molecular evidence.
Insights
Germline mutations in genes like VHL, FH, and SDHB are linked to kidney cancers. This study identifies uncommon gene mutations (MUTYH, NF2, BARD1) in renal neoplasms, expanding knowledge of their genetic basis and clinical impact.
Area of Science:
- Genetics
- Oncology
- Nephrology
Background:
- Germline mutations are increasingly recognized in various renal neoplasm types.
- Limited understanding exists regarding the full spectrum of germline mutations in kidney cancers.
- The fifth edition of the World Health Organization Classification highlights germline mutations in renal neoplasms.
Purpose of the Study:
- To expand the understanding of renal neoplasms associated with germline mutations.
- To identify both common and uncommon germline mutations in a cohort of renal tumors.
- To investigate the clinical and pathological spectrum of renal neoplasms harboring germline mutations.
Main Methods:
- Next-generation sequencing was performed on 284 renal neoplasms.
- Fifteen tumors with identified germline mutations were retrieved for further analysis.
- Analysis included well-known genes (VHL, FH, SDHB, FLCN, TSC1) and less common ones (MUTYH, NF2, BARD1).
Main Results:
- Identified clear cell renal cell carcinoma (RCC) with FH germline mutation.
- Observed succinate dehydrogenase (SDH)-deficient RCC with high-grade transformation.
- Found that uncommon germline mutations (MUTYH, NF2, BARD1) were associated with diverse renal entities, including those with favorable and adverse outcomes.
Conclusions:
- Germline mutations in genes uncommon in renal neoplasms, such as MUTYH, NF2, and BARD1, can contribute to kidney cancer pathogenesis.
- While not definitive for entity diagnosis, these mutations offer insights into tumor development.
- Diagnosis of renal neoplasms requires a comprehensive approach integrating morphology, immunohistochemistry, and molecular data.
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