Département de Génétique (Department of Genetics), Institut Curie, Paris, France.
Département de Génétique (Department of Genetics), Institut Curie, Paris, France; Paris Sciences & Lettres Research University, Paris, France.
Eur J Med Genet. 2022 Jan;65(1):104385. doi: 10.1016/j.ejmg.2021.104385. Epub 2021 Nov 11.
The MUTYH gene encodes a DNA glycosylase that prevents G:C→T:A transversions. Patients with biallelic pathogenic germline MUTYH variants develop an adenomatous polyposis called MUTYH-associated polyposis (MAP). Endometrial cancers have been reported in patients with MAP, but the role of MUTYH loss of function in the oncogenesis remains unclear. We report for the first time a case of endometrial carcinoma with excess of G:C→T:A transversions in a 61-year-old patient with MAP. Single nucleotide variants of interest, Tumor Mutational Burden (TMB) and somatic mutation profile were obtained from Next-Generation Sequencing (NGS). The Tumor-Infiltrating Lymphocyte (TIL) level and immune infiltrate phenotype were assessed. The endometrial cancer had a high TMB (31.5 variants/Mb) with enrichment in G:C→T:A transversions and the presence of a driver pathogenic variant c.34G>T, p.(Gly12Cys) in KRAS, suggesting a role of MUTYH loss of function in oncogenesis. MUTYH loss of function could be involved in endometrial cancer in patients with MAP.
MUTYH 基因编码一种 DNA 糖苷酶，可防止 G:C→T:A 颠换。具有双等位基因致病性种系 MUTYH 变异的患者会发展为称为 MUTYH 相关息肉病 (MAP) 的腺瘤性息肉病。已有报道称 MAP 患者会发生子宫内膜癌，但 MUTYH 功能丧失在肿瘤发生中的作用仍不清楚。我们首次报道了一例 61 岁 MAP 患者伴 G:C→T:A 颠换过多的子宫内膜癌。从下一代测序 (NGS) 中获得了感兴趣的单核苷酸变体、肿瘤突变负担 (TMB) 和体细胞突变谱。评估了肿瘤浸润淋巴细胞 (TIL) 水平和免疫浸润表型。子宫内膜癌 TMB 较高 (31.5 个变异/Mb)，G:C→T:A 颠换丰富，存在 KRAS 中的驱动致病性变异 c.34G>T，p.(Gly12Cys)，提示 MUTYH 功能丧失在肿瘤发生中的作用。MUTYH 功能丧失可能与 MAP 患者的子宫内膜癌有关。
