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

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.

journal_name

Cancer Lett

journal_title

Cancer letters

authors

Tricarico R,Bet P,Ciambotti B,Di Gregorio C,Gatteschi B,Gismondi V,Toschi B,Tonelli F,Varesco L,Genuardi M

doi

10.1016/j.canlet.2008.09.022

subject

Has Abstract

pub_date

2009-02-18 00:00:00

pages

266-70

issue

2

eissn

0304-3835

issn

1872-7980

pii

S0304-3835(08)00791-X

journal_volume

274

pub_type

杂志文章

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