Synapse - Germline SDHA mutations in children and adults with cancer

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). Immunohistochemical 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. © 2018 Dubard Gault et al.
Keywords:	immunohistochemistry; adult; child; clinical article; preschool child; aged; middle aged; young adult; gene sequence; exon; gene deletion; cancer patient; endometrium carcinoma; gene; gene targeting; gastrointestinal stromal tumor; melanoma; cohort analysis; renal cell carcinoma; patient identification; cancer center; neuroblastoma; heterozygosity; gene loss; prostate adenocarcinoma; uterus cancer; genetic screening; transitional cell carcinoma; stomach carcinoma; colon adenocarcinoma; triple negative breast cancer; germline mutation; sdha gene; human; article; malignant neoplasm
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
DOI:	10.1101/mcs.a002584
PUBMED:	30068732
PROVIDER:	scopus
PMCID:	PMC6071569
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85063300760&doi=10.1101%2fmcs.a002584&partnerID=40&md5=a78779d2e77ff265e33f8cfab136a1ea
Notes:	Article -- Export Date: 1 May 2019 -- Source: Scopus