Analysis of mutations in TP53, APC, K-ras, and DCC genes in the non-dysplastic mucosa of patients with inflammatory bowel disease

Background and aims Patients with ulcerative colitis (UC) and Crohn's disease (CD) have a high risk for colorectal cancer (CRC). To understand the molecular basis of colitis-associated CRC, we analyzed alterations in TP53, APC, K-ras, and DCC genes in the non-dysplastic UC and CD colon. Materia...

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Published in:	International journal of colorectal disease Vol. 24; no. 10; pp. 1141 - 1148
Main Authors:	Rapozo, Davy Carlos Mendes, Grinmann, Ana Braunstein, Carvalho, Ana Teresa Pugas, de Souza, Heitor Siffert P, Soares-Lima, Sheila Coelho, de Almeida Simão, Tatiana, de Paiva, Daurita, Abby, Flávio, Albano, Rodolpho Mattos, Pinto, Luiz Felipe Ribeiro
Format:	Journal Article
Language:	English
Published:	Berlin/Heidelberg Berlin/Heidelberg : Springer-Verlag 01-10-2009 Springer-Verlag Springer Springer Nature B.V
Subjects:	Adenomatous Polyposis Coli Protein - genetics Adolescent Adult Aged Base Sequence Biological and medical sciences Codon - genetics Colitis, Ulcerative - genetics Colitis, Ulcerative - pathology Crohn Disease - genetics Crohn Disease - pathology DCC Receptor DNA Mutational Analysis Female Gastroenterology Gastroenterology. Liver. Pancreas. Abdomen Hepatology Humans Inflammatory bowel disease Inflammatory Bowel Diseases - genetics Internal Medicine Intestinal Mucosa - metabolism Intestinal Mucosa - pathology Male Medical sciences Medicine Medicine & Public Health Middle Aged Molecular Sequence Data Mutation - genetics Original Article Other diseases. Semiology Point Mutation - genetics Proctology Proto-Oncogene Proteins - genetics Proto-Oncogene Proteins p21(ras) ras Proteins - genetics Receptors, Cell Surface - genetics Stomach. Duodenum. Small intestine. Colon. Rectum. Anus Surgery Tumor Suppressor Protein p53 - genetics Tumor Suppressor Proteins - genetics Young Adult Non-dysplastic mucosa Crohn's disease Ulcerative colitis Human Mucosa Inflammatory disease Crohn disease Non-dysplastac mucosa APC K-ras Gastroenterology Digestive diseases Intestinal disease Mutation Onc gene Ras gene TP53
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Summary:	Background and aims Patients with ulcerative colitis (UC) and Crohn's disease (CD) have a high risk for colorectal cancer (CRC). To understand the molecular basis of colitis-associated CRC, we analyzed alterations in TP53, APC, K-ras, and DCC genes in the non-dysplastic UC and CD colon. Materials and methods Endoscopic biopsies were collected from six predefined colon sites of 35 UC and 12 CD patients for DNA extraction and genetic analysis. Results A mutation was found in codon 1141 of the APC gene of two CD patients, being somatic in one and germinative in the other. The mutation seen in both patients was a base exchange of thymine for cytosine, resulting in an exchange of leucine for serine. We did not detect any mutations in the other samples analyzed. Conclusions Mutations in APC gene may occur in the non-dysplastic CD mucosa of patients with disease for more than 10 years. The follow-up of these patients will show the likelihood of mutant APC progressing to CRC in CD. Further analysis will be required for evaluating the impact of these findings in the context of cancer surveillance in inflammatory bowel disease.
Bibliography:	http://dx.doi.org/10.1007/s00384-009-0748-5 ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2
ISSN:	0179-1958 1432-1262
DOI:	10.1007/s00384-009-0748-5