琥珀酸脱氢酶 c.914T > C（p.Phe305Ser）是一种与遗传性平滑肌瘤病和肾细胞癌综合征相关的致病性变异。
Fumarate hydratase c.914T > C (p.Phe305Ser) is a pathogenic variant associated with hereditary leiomyomatosis and renal cell cancer syndrome.
机构信息
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York City, NY, USA.
Niehaus Center for Inherited Cancer Genomics, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York City, NY, USA.
出版信息
Mol Genet Genomic Med. 2020 Aug;8(8):e1293. doi: 10.1002/mgg3.1293. Epub 2020 May 28.
BACKGROUND
Hereditary leiomyomatosis and renal cell cancer syndrome (HLRCC), caused by heterozygous germline pathogenic variants in the FH, confers an increased risk for cutaneous and uterine leiomyomas and renal cancer.
METHODS
About 13,722 advanced cancer patients, including 560 with renal cell carcinoma, had germline analysis performed in the context of tumor-normal sequencing under an IRB approved protocol.
RESULTS
We report two unrelated individuals with early onset kidney cancer who both carried the c.914C > T (p.Phe305Ser) germline variant in the FH. Both tumors exhibited loss of FH staining by immunohistochemistry and/or positive 2SC staining. Subsequent familial testing discovered that a daughter of a proband who carried the variant had both cutaneous and uterine leiomyomas.
CONCLUSION
This combination of evidence suggests that the FH c.914C > T (p.Phe305Ser) is pathogenic for HLRCC.
背景
由 FH 中的杂合种系致病性变异引起的遗传性平滑肌瘤病和肾细胞癌综合征（HLRCC），会增加皮肤和子宫平滑肌瘤以及肾癌的风险。
方法
根据经 IRB 批准的方案，在肿瘤-正常测序的背景下，对大约 13722 名晚期癌症患者（包括 560 名肾细胞癌患者）进行了种系分析。
结果
我们报告了两名患有早期肾癌的无血缘关系的个体，他们均携带 FH 中的 c.914C>T(p.Phe305Ser)种系变异。两种肿瘤的免疫组织化学染色均显示 FH 缺失，或 2SC 染色阳性。随后的家族测试发现，一位携带该变异的先证者的女儿患有皮肤和子宫平滑肌瘤。
结论
这组证据表明，FH c.914C>T(p.Phe305Ser) 是 HLRCC 的致病因素。
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