Loading...
Interaction of germline variants in a family with a history of early-onset clear cell renal cell carcinoma
Nicolas, Emmanuelle Demidova, Elena V. Iqbal, Waleed Serebriiskii, Ilya G. Vlasenova, Ramilia Ghatalia, Pooja Zhou, Yan Rainey, Kim
Nicolas, Emmanuelle
Demidova, Elena V.
Iqbal, Waleed
Serebriiskii, Ilya G.
Vlasenova, Ramilia
Ghatalia, Pooja
Zhou, Yan
Rainey, Kim
Citations
Altmetric:
Genre
Journal article
Date
2019-01-24
Advisor
Committee member
Department
Cancer and Cellular Biology
Permanent link to this record
Collections
Research Projects
Organizational Units
Journal Issue
DOI
http://dx.doi.org/10.1002/mgg3.556
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.
Description
Citation
Nicolas E, Demidova EV, Iqbal W, Serebriiskii IG, Vlasenova R, Ghatalia P, et al. Interaction of germline variants in a family with a history of early-onset clear cell renal cell carcinoma. Mol Genet Genomic Med. 2019 Jan 24;7:e556. doi:10.1002/mgg3.556.
Citation to related work
Wiley Open Access
Has part
Molecular Genetics and Genomic Medicine, Vol. 7, Iss. 3
ADA compliance
For Americans with Disabilities Act (ADA) accommodation, including help with reading this content, please contact scholarshare@temple.edu