Germline mutations in children and adults with cancer.

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 mutations. Using targeted sequencing covering the cancer census genes, we identified 10 patients with germline mutations. Cancer diagnoses for these patients carrying germline mutations included neuroblastoma ( = 1), breast ( = 1), colon ( = 1), renal ( = 1), melanoma and uterine ( = 1), prostate ( = 1), endometrial ( = 1), bladder ( = 1), and gastrointestinal stromal tumor (GIST) ( = 2). Immunohistochemical staining and assessment of patient tumors for second hits and loss of heterozygosity in confirmed GIST as an -associated tumor and suggests germline mutations may be a driver in neuroblastoma tumorigenesis.