Germline SDHA mutations in children and adults with cancer.
Germline SDHA mutations in children and adults with cancer.
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DOI：
10.1101/mcs.a002584
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发表时间：
2018-08
影响因子：
1.8
通讯作者：
Walsh MF
中科院分区：
文献类型：
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作者：
Dubard Gault M;Mandelker D;DeLair D;Stewart CR;Kemel Y;Sheehan MR;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 EC;Ceyhan-Birsoy O;Zhang L;Kohlman W;Schiffman J;Stadler Z;Birsoy K;Kung A;Offit K;Walsh MF
琥珀酸脱氢酶复合体基因突变易患家族性副神经节瘤-嗜铬细胞瘤综合征(FPG)和胃肠道间质瘤(GIST)。在这里，我们描述了在纪念斯隆-凯特琳癌症中心接受不可知胚系测试的癌症患者，发现他们携带种系SDHA突变。使用覆盖癌症普查基因的靶向测序，我们确定了10名患有SDHA种系突变的患者。这些携带SDHA胚系突变的患者的癌症诊断包括神经母细胞瘤(n=1)、乳腺(n=1)、结肠(n=1)、肾脏(n=1)、黑色素瘤和子宫(n=1)、前列腺(n=1)、子宫内膜(n=1)、膀胱(n=1)和胃肠道间质瘤(GIST)(n=2)。免疫组织化学染色和对患者肿瘤的二次命中和SDHA杂合性丢失的评估证实了GIST是SDHA相关的肿瘤，并提示SDHA种系突变可能是神经母细胞瘤肿瘤发生的驱动因素。
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.