Low Gene Dosage of Cdc42 Is Not Associated with Protein Dysfunction in Patients with Colorectal Cancer

Matías González-Quiroz, Ximena Calderón, Ingrid Oyarzún, Claudia Hoepfner, Andrés Azócar, Adam Aguirre, Karin Álvarez, Rodrigo Quera, Francisco López-Köstner, Jaime Meléndez

Research output: Contribution to journalArticlepeer-review

Abstract

High incidence of Rho Cdc42-GTPase overexpression has been found in Colorectal Cancer (CRC) samples, suggesting its potential role in tumor development. However, no conclusive studies have shown the lack of mutations and/or copy number of Cdc42 gene in this type of samples. To understand mutation/deletion and copy number status of Cdc42 gene, CRC patients were evaluated for both parameters. More than Cdc42 mutants, single-nucleotide variants were found. Analysis of regions flanking the Cdc42 gene showed allelic imbalance; 58.7% were loss of heterozygosity (LOH) positive and 14.8% presented microsatellite instability. The highest LOH percentage was located between microsatellite markers D1S199 and D1S2674, where the Cdc42 gene is located. No association between gender, age, and tumor stage was found. LOH validation through gene dosage analysis showed most CRC patients with allelic imbalance also presented a low gene dosage of Cdc42, although equal amounts of Cdc42 mRNA were detected in all samples. Although changes in Cdc42 expression were not found in any condition, Cdc42 activation was different between high and normal gene dosage samples, but not between samples with normal and low copy number. Low dosage of Cdc42 was also not related to changes in methylation status at the Cdc42 promoter region. Results suggest that low copy of Cdc42 gene is not associated with Cdc42 protein dysfunction in CRC patients.

Original languageEnglish
Pages (from-to)819-827
Number of pages9
JournalDNA and Cell Biology
Volume35
Issue number12
DOIs
StatePublished - Dec 2016
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2016 Mary Ann Liebert, Inc.

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