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New Target Genes in Endometrial Tumors Show a Role for the Estrogen‐Receptor Pathway in Microsatellite‐Unstable Cancers
Author(s) -
Ferreira Ana M.,
Tuominen Iina,
Sousa Sónia,
Gerbens Frans,
DijkBos Krista,
Osinga Jan,
Kooi Krista A.,
Sanjabi Bahram,
Esendam Chris,
Oliveira Carla,
Terpstra Peter,
Hardonk Menno,
Sluis Tineke,
Zazula Monika,
Stachura Jerzy,
Zee Ate G.,
Hollema Harry,
Sijmons Rolf H.,
Aaltonen Lauri A.,
Seruca Raquel,
Hofstra Robert M. W.,
Westers Helga
Publication year - 2014
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.22700
Subject(s) - biology , microsatellite instability , gene , endometrial cancer , dna mismatch repair , cancer research , genetics , mutation , cancer , microsatellite , dna repair , allele
Microsatellite instability ( MSI ) in tumors results in an accumulation of mutations in (target) genes. Previous studies suggest that the profile of target genes differs according to tumor type. This paper describes the first genome‐wide search for target genes for mismatch repair‐deficient endometrial cancers. Genes expressed in normal endometrium containing coding repeats were analyzed for mutations in tumors. We identified 44 possible genes of which seven are highly mutated (>15%). Some candidates were also found mutated in colorectal and gastric tumors. The most frequently mutated gene, NRIP 1 encoding nuclear receptor‐interacting protein 1, was silenced in an endometrial tumor cell line and expression microarray experiments were performed. Silencing of NRIP 1 was associated with differences in the expression of several genes in the estrogen‐receptor network. Furthermore, an enrichment of genes related to cell cycle (regulation) and replication was observed. We present a new profile of target genes, some of them tissue specific, whereas others seem to play a more general role in MSI tumors. The high‐mutation frequency combined with the expression data suggest, for the first time, an involvement of NRIP 1 in endometrial cancer development.