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Germline SDHA mutations in children and adults with cancer

2018; Cold Spring Harbor Laboratory Press; Volume: 4; Issue: 4 Linguagem: Inglês

10.1101/mcs.a002584

2373-2873

Marianne Dubard Gault, Diana Mandelker, Deborah F. DeLair, Carolyn Stewart, Yelena Kemel, Margaret Sheehan, Beth Siegel, Jennifer A. Kennedy, Vanessa Marcell, Angela G. Arnold, Hikmat Al‐Ahmadie, Shakeel Modak, Mark E. Robson, Neerav Shukla, Stephen S. Roberts, Joseph Vijai, Sabine Topka, Alex Kentsis, Karen A. Cadoo, Maria I. Carlo, Alicia Latham Schwark, Ed Reznik, Renzo G. DiNatale, Jaclyn F. Hechtman, Ester Borrás Flores, Sowmaya Jairam, Ciyu Yang, Yirong Li, Erol C. Bayraktar, Özge Ceyhan-Birsoy, Liying Zhang, Wendy Kohlman, Joshua D. Schiffman, Zsofia K. Stadler, Kıvanç Birsoy, Andrew L. Kung, Kenneth Offit, Michael F. Walsh,

Cancer, Hypoxia, and Metabolism

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.