Endometrial cancer and somatic G>T KRAS transversion in patients with constitutional MUTYH biallelic mutations

Rossella Tricarico, Paola Bet, Benedetta Ciambotti, Carmela Di Gregorio, Beatrice Gatteschi, Viviana Gismondi, Benedetta Toschi, Francesco Tonelli, Liliana Varesco, Maurizio Genuardi

Research output: Contribution to journalArticlepeer-review

Abstract

MUTYH-associated polyposis (MAP) is an autosomal recessive condition predisposing to colorectal cancer, caused by constitutional biallelic mutations in the base excision repair (BER) gene MUTYH. Colorectal tumours from MAP patients display an excess of somatic G>T mutations in the APC and KRAS genes due to defective BER function. To date, few extracolonic manifestations have been observed in MAP patients, and the clinical spectrum of this condition is not yet fully established. Recently, one patient with a diagnosis of endometrial cancer and biallelic MUTYH mutations has been described. We here report on two additional unrelated MAP patients with biallelic MUTYH germline mutations who developed endometrioid endometrial carcinoma. The endometrial tumours were evaluated for PTEN, PIK3CA, KRAS, BRAF and CTNNB1 mutations. A G>T transversion at codon 12 of the KRAS gene was observed in one tumour. A single 1bp frameshift deletion of PTEN was observed in the same sample. Overall, these findings suggest that endometrial carcinoma is a phenotypic manifestations of MAP and that inefficient repair of oxidative damage can be involved in its pathogenesis.

Original languageEnglish
Pages (from-to)266-270
Number of pages5
JournalCancer Letters
Volume274
Issue number2
DOIs
Publication statusPublished - Feb 18 2009

Keywords

  • Base excision repair
  • Colorectal cancer
  • Lynch syndrome
  • MAP
  • Polyposis

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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