Open AccessFunctional succinate dehydrogenase deficiency is a common adverse feature of clear cell renal cancer
Author(s) -
Ritesh Kumar Aggarwal,
Rebecca A. Luchtel,
Venkata R. Machha,
Alexander Tischer,
Yiyu Zou,
Kith Pradhan,
Nadia Ashai,
Nandini Ramachandra,
Joseph Albanese,
Jung-In Yang,
Xiaoyang Wang,
Srinivas Aluri,
Shanisha Gordon,
Ahmed Aboumohamed,
Benjamin A. Gartrell,
Sassan Hafizi,
James Pullman,
Niraj Shenoy
Publication year - 2021
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2106947118
Subject(s) - sdhd , succinate dehydrogenase , sdhb , cancer research , clear cell renal cell carcinoma , biology , cancer , endocrinology , medicine , mitochondrion , microbiology and biotechnology , biochemistry , germline mutation , renal cell carcinoma , mutation , genetics , gene
Significance This study demonstrates that underexpression of succinate dehydrogenase (SDH) subunits resulting in accumulation of oncogenic succinate is a common, adverse, epigenetic modulating feature in clear cell renal cell carcinoma (ccRCC), during pathogenesis and progression. The study sheds light on the mechanisms of down-regulation of SDH subunits in ccRCC and deciphers the consequent oncogenic effects. It shows that functional SDH deficiency is a common feature of ccRCC (∼80% of all kidney cancers), and not just limited to the 0.05 to 0.5% of kidney cancers with germline SDH mutations.