Who takes the lead in the development of ulcerative colitis-associated colorectal cancers: mutator, suppressor, or methylator pathway?

• Type: Article in International Scientific Journal
• Date: 2005

Authors

Maia, L (Author) Other; Dinis, J (Author) Other; Cravo, M (Author) Other; Claro, I (Author) Other; Baltazar, C (Author) Other; Fonseca, I (Author) Other; Veloso, T (Author) Other; Capelinha, AF (Author) Other; Carneiro F (Author) FMUP; Nobre Leitao, C (Author) Other

Journal

Title: Cancer Genetics and Cytogenetics

Vol. 162

Pages: 68-73

ISSN: 0165-4608

Publisher: Elsevier B.V.

Indexing

ISI Web of Knowledge - 15 Citations

Scopus - 15 Citations

Other information

Authenticus ID: P-000-101

DOI: 10.1016/j.cancergencyto.2005.02.017

Abstract (EN): Although several genetic alterations have been identified in patients with ulcerative colitis (UC), it remains unclear whether these changes indicate an increased risk for malignancy. This paper analyzes the involvement of suppressor, mutator, and methylator pathways in malignant transformation associated with UC. A total of 60 colonic samples (47 affected non-neoplastic mucosa, 7 dysplasia, and 6 carcinoma) from 51 UC patients were analyzed for 22 microsatellite markers. p53 gene exons 5-8 were analyzed by single-strand conformational polymorphism, and APC gene by denaturing gradient gel electrophoresis (exons 1-14) and protein truncation test (exon 15). Methylation studies for MLH1 and CSPG2 genes were also performed. Microsatellite instability was absent in all samples whereas allelic imbalance (AI) and loss of heterozygosity (LOH) were detected mainly in samples with neoplastic transformation (P < 0.0001). AI and/or LOH at loci located on chromosomes 5, 9, and 18 were significantly more frequent in neoplastic samples (P < 0.01), as were TP53 gene mutations (P < 0.007). A single mutation was detected for APC gene in a cancer sample. MLH1 gene methylation was absent in all analyzed samples, whereas CSPG2 gene methylation was detected in a single non-neoplastic sample. Our results suggest that the suppressor pathway plays the main role in UC associated tumorigenic progression. LOH at specific loci located on chromosomes 5, 9, and 18 appears to be specifically associated with malignancy risk.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 6