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.
Keywords: MUTYH; Molecular genetics; Mutational signature; NGS; Oncogenetics.
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