International journal of colorectal disease · 2009
Analysis of mutations in TP53, APC, K-ras, and DCC genes in the non-dysplastic mucosa of patients with inflammatory bowel disease.
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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
Аннотация
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.
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.
Предметные рубрики MeSH
Adenomatous Polyposis Coli ProteinAdolescentAdultAgedBase SequenceCodonColitis, UlcerativeCrohn DiseaseDCC ReceptorDNA Mutational AnalysisFemaleHumansInflammatory Bowel DiseasesIntestinal MucosaMaleMiddle AgedMolecular Sequence DataMutationPoint MutationProto-Oncogene ProteinsProto-Oncogene Proteins p21(ras)Receptors, Cell SurfaceTumor Suppressor Protein p53Tumor Suppressor ProteinsYoung Adultras Proteins