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Cold Spring Harb Mol Case Stud. 2018 Aug 1;4(4). pii: a002584. doi: 10.1101/mcs.a002584. Print 2018 Aug.

Germline SDHA mutations in children and adults with cancer.

Author information

1
Graduate Education Memorial, Memorial Sloan Kettering Cancer Center and Weill Cornell Genetics, New York, New York 10065, USA.
2
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA.
3
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA.
4
Niehaus Center for Inherited Cancer Genomics, Clinical Genetics Service, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA.
5
Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA.
6
Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA.
7
Rockefeller University, New York, New York 10021, USA.
8
Family Cancer Assessment Clinic, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah 84112, USA.

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.

KEYWORDS:

clear cell renal cell carcinoma; gastrointestinal stroma tumor; neoplasm of the breast; neuroblastoma

PMID:
30068732
PMCID:
PMC6071569
DOI:
10.1101/mcs.a002584
[Indexed for MEDLINE]
Free PMC Article

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