Journal article
Interaction of germline variants in a family with a history of early-onset clear cell renal cell carcinoma
Molecular genetics & genomic medicine, v 7(3), 556
Mar 2019
PMID: 30680959
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Background Identification of genetic factors causing predisposition to renal cell carcinoma has helped improve screening, early detection, and patient survival. Methods We report the characterization of a proband with renal and thyroid cancers and a family history of renal and other cancers by whole-exome sequencing (WES), coupled with WES analysis of germline DNA from additional affected and unaffected family members. Results This work identified multiple predicted protein-damaging variants relevant to the pattern of inherited cancer risk. Among these, the proband and an affected brother each had a heterozygous Ala45Thr variant in SDHA, a component of the succinate dehydrogenase (SDH) complex. SDH defects are associated with mitochondrial disorders and risk for various cancers; immunochemical analysis indicated loss of SDHB protein expression in the patient's tumor, compatible with SDH deficiency. Integrated analysis of public databases and structural predictions indicated that the two affected individuals also had additional variants in genes including TGFB2, TRAP1, PARP1, and EGF, each potentially relevant to cancer risk alone or in conjunction with the SDHA variant. In addition, allelic imbalances of PARP1 and TGFB2 were detected in the tumor of the proband. Conclusion Together, these data suggest the possibility of risk associated with interaction of two or more variants.
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Details
- Title
- Interaction of germline variants in a family with a history of early-onset clear cell renal cell carcinoma
- Creators
- Emmanuelle Nicolas - Fox Chase Cancer CenterElena Demidova - Fox Chase Cancer CenterWaleed Iqbal - Fox Chase Cancer CenterIlya G. Serebriiskii - Kazan Federal UniversityRamilia Vlasenkova - Kazan Federal UniversityPooja Ghatalia - Fox Chase Cancer CenterYan Zhou - Fox Chase Cancer CenterKim Rainey - Fox Chase Cancer CenterAndrea F. Forman - Fox Chase Cancer CenterRoland L. Dunbrack - Fox Chase Cancer CenterErica A. Golemis - Fox Chase Cancer CenterMichael J. Hall - Fox Chase Cancer CenterMary B. Daly - Fox Chase Cancer CenterSanjeevani Arora - Fox Chase Cancer Center
- Publication Details
- Molecular genetics & genomic medicine, v 7(3), 556
- Publisher
- Wiley
- Number of pages
- 18
- Grant note
- Russian Government P30 CA006927 / NCI; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) W81XWH-18-1-0148 / DOD; United States Department of Defense R01 DK108195; R35 GM122517; T32 CA009035 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology; Pharmacology and Physiology
- Web of Science ID
- WOS:000461447100028
- Scopus ID
- 2-s2.0-85060579297
- Other Identifier
- 991022083948804721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Genetics & Heredity