Researchers of the group of Colorectal Cancer Prevention and Control

Cancer Program of the Catalan Institute of Oncology and the Bellvitge Biomedical Research Institute (IDIBELL-ICO), led by Victor Moreno have identified mutations in the gene AMER1, in about 10% of colon tumors analyzed.

With the objective of characterizing the set of mutations accumulated tumor exome (the coding portion of the genome) of 42 samples from patients with colon cancer he was sequenced by techniques ultrasecuenciación (Next Generation Sequencing). As a result, a high heterogeneity between patients was observed; each showing a characteristic mutational pattern. However, about 10% of the analyzed tumors had mutations in the gene AMER1. Most of these mutations generate a stop codon (or codon), leading to the generation of a truncated protein and generally inoperative. This result was validated on an additional set of 553 colorectal tumors.

AMER1 is a gene located on the X chromosome that encodes a highly conserved membrane protein. That one helps the beta-catenin degradation and therefore has a regulatory role in Wnt pathway. Furthermore, AMER1 helps maintain cellular integrity and maintaining the membrane localization of the APC gene. Therefore, the loss of this gene may be related to the tumorigenesis through the loss of regulation of these functions. It is interesting to highlight that as it’s located on the X chromosome, the loss of a single allele in the case of totally inactive gene men.

In addition, the group had previously characterized the tumors studied at the level of RNA expression, methylation and variation in the number of copies of DNA (for more information can visit the website www.colonomics.org). Although to a lesser extent, tumors that had lost AMER1 gene expression by mechanisms of methylation and loss of an entire chromosome arm were found. Also, analysis of gene expression data that is used to characterize the samples studied phenotypically suggests that tumors lose expression of AMER1 undergoes inactivation of the Wnt pathway. This finding opens the way to further investigate the role of AMER1 as tumor suppressor gene in sporadic colon cancer.

In this study involved researchers from IDIBELL, ICO and CNAG, where they carried out the sequencing of tumors and it has been published in the journal Clinical Cancer Research.

Sanz-Pamplona R, Lopez-Doriga A, Paré-Brunet L, Lázaro K, Bellido F, Alonso MH, Aussó S, Guinó E, Beltrán S, Castro-Giner F, Gut M, Sanjuan X, Closa A, Cordero D, Morón-Duran FD, Soriano A, Salazar R, Valle L, Moreno V. Exome Sequencing Reveals AMER1 as a Frequently Mutated Gene in Colorectal Cancer.

Clinical Cancer Research

2015; 21(20):4709-18. doi: 10.1158/1078-0432.CCR-15-0159