title: Low Gene Dosage of Cdc42 Is Not Associated with Protein Dysfunction in Patients with Colorectal Cancer.
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.
authors.affiliation: 1 Deparment of Pharmacy, Faculty of Chemistry, Pontificia Universidad Católica de Chile, Santiago de Chile, Chile .
authors.forename: Matías
authors.initials: M
authors.lastname: González-Quiroz
authors.affiliation: 1 Deparment of Pharmacy, Faculty of Chemistry, Pontificia Universidad Católica de Chile, Santiago de Chile, Chile .
authors.forename: Ximena
authors.initials: X
authors.lastname: Calderón
authors.affiliation: 1 Deparment of Pharmacy, Faculty of Chemistry, Pontificia Universidad Católica de Chile, Santiago de Chile, Chile .
authors.forename: Ingrid
authors.initials: I
authors.lastname: Oyarzún
authors.affiliation: 1 Deparment of Pharmacy, Faculty of Chemistry, Pontificia Universidad Católica de Chile, Santiago de Chile, Chile .
authors.forename: Claudia
authors.initials: C
authors.lastname: Hoepfner
authors.affiliation: 1 Deparment of Pharmacy, Faculty of Chemistry, Pontificia Universidad Católica de Chile, Santiago de Chile, Chile .
authors.forename: Andrés
authors.initials: A
authors.lastname: Azócar
authors.affiliation: 1 Deparment of Pharmacy, Faculty of Chemistry, Pontificia Universidad Católica de Chile, Santiago de Chile, Chile .
authors.forename: Adam
authors.initials: A
authors.lastname: Aguirre
authors.affiliation: 2 Laboratorio de Oncología y Genética Molecular, Unidad de Coloproctología , Clínica Las Condes, Santiago de Chile, Chile .
authors.forename: Karin
authors.initials: K
authors.lastname: Álvarez
authors.affiliation: 3 Gastroenterology Service, Clínica Las Condes , Santiago de Chile, Chile .
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Quera
authors.affiliation: 2 Laboratorio de Oncología y Genética Molecular, Unidad de Coloproctología , Clínica Las Condes, Santiago de Chile, Chile .
authors.forename: Francisco
authors.initials: F
authors.lastname: López-Köstner
authors.affiliation: 1 Deparment of Pharmacy, Faculty of Chemistry, Pontificia Universidad Católica de Chile, Santiago de Chile, Chile .
authors.forename: Jaime
authors.initials: J
authors.lastname: Meléndez
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D003106:Colon / Q000378:metabolism / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D018628:Gene Dosage; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009367:Neoplasm Staging; D012189:Retrospective Studies; D017384:Sequence Deletion; D020764:cdc42 GTP-Binding Protein / Q000172:deficiency / Q000235:genetics*
chemical_list: D020764:cdc42 GTP-Binding Protein