Germline SDHA mutations in children and adults with cancer Journal Article


Authors: Dubard Gault, M.; Mandelker, D.; DeLair, D.; Stewart, C. R.; Kemel, Y.; Sheehan, M. R.; Siegel, B.; Kennedy, J.; Marcell, V.; Arnold, A.; Al-Ahmadie, H.; Modak, S.; Robson, M.; Shukla, N.; Roberts, S.; Vijai, J.; Topka, S.; Kentsis, A.; Cadoo, K.; Carlo, M.; Latham Schwark, A.; Reznik, E.; Dinatale, R.; Hechtman, J.; Borras Flores, E.; Jairam, S.; Yang, C.; Li, Y.; Bayraktar, E. C.; Ceyhan-Birsoy, O.; Zhang, L.; Kohlman, W.; Schiffman, J.; Stadler, Z.; Birsoy, K.; Kung, A.; Offit, K.; Walsh, M. F.
Article Title: Germline SDHA mutations in children and adults with cancer
Abstract: Mutations in succinate dehydrogenase complex genes predispose to familial paraganglioma-pheochromocytoma syndrome (FPG) and gastrointestinal stromal tumors (GIST). Here we describe cancer patients undergoing agnostic germline testing at Memorial Sloan Kettering Cancer Center and found to harbor germline SDHA mutations. Using targeted sequencing covering the cancer census genes, we identified 10 patients with SDHA germline mutations. Cancer diagnoses for these patients carrying SDHA germline mutations included neuroblastoma (n = 1), breast (n = 1), colon (n = 1), renal (n = 1), melanoma and uterine (n = 1), prostate (n = 1), endometrial (n = 1), bladder (n = 1), and gastrointestinal stromal tumor (GIST) (n = 2). lmmunohistochemical staining and assessment of patient tumors for second hits and loss of heterozygosity in SDHA confirmed GIST as an SDHA-associated tumor and suggests SDHA germline mutations may be a driver in neuroblastoma tumorigenesis.
Keywords: immunohistochemistry; sequence; tumor; expression; men; gene-mutations; cloning; paragangliomas; flavoprotein subunit; cytochrome-b558
Journal Title: Cold Spring Harbor Molecular Case Studies
Volume: 4
Issue: 4
ISSN: 2373-2873
Publisher: Cold Spring Harbor Laboratory Press  
Date Published: 2018-08-01
Start Page: a002584
Language: English
ACCESSION: WOS:000450957400002
DOI: 10.1101/mcs.a002584
PROVIDER: wos
PMCID: PMC6071569
PUBMED: 30068732
Notes: Article -- Source: Wos
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