Genetic alterations in sporadic and Crohn's-associated adenocarcinomas of the small intestine

• Published in: Gastroenterology (New York, N.Y. 1943) Vol. 113; no. 1; pp. 127 - 135
• Main Authors: Rashid, A, Hamilton, SR
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01-07-1997; Elsevier
• Subjects: Adenocarcinoma - complications; Adenocarcinoma - genetics; Adenoma - complications; Adenoma - genetics; Adult; Aged; Biological and medical sciences; Chromosome Deletion; Chromosomes, Human, Pair 17; Chromosomes, Human, Pair 18; Chromosomes, Human, Pair 5; Colorectal Neoplasms - genetics; Crohn Disease - complications; Crohn Disease - genetics; Female; Gastroenterology. Liver. Pancreas. Abdomen; Genes, p53 - genetics; Genes, ras - genetics; Humans; Intestinal Neoplasms - complications; Intestinal Neoplasms - genetics; Male; Medical sciences; Middle Aged; Point Mutation; Polymerase Chain Reaction; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumors; Human; Immunohistochemistry; Carcinoma; Transforming growth factor β; Gut; Alteration; Malignant tumor; Inflammatory disease; Result; Pathology; Crohn disease; TP53 Gene; Immunological investigation; Digestive diseases; Genetics; Intestinal disease; Complication; Mutation
• ISSN: 0016-5085; 1528-0012
• DOI: 10.1016/S0016-5085(97)70087-8

BACKGROUND & AIMS: Small intestinal carcinomas are rare but occur with increased incidence in Crohn's disease. The aim of this study was to elucidate the genetic alterations.
METHODS: Mutations and deletions involved in colorectal carcinoma were studied in sporadic and Crohn's- associated intestinal carcinomas and precursors.
RESULTS: c-K-ras mutations were present in all four sporadic carcinomas with contiguous adenomas, in only 18% without adenomas (P = 0.01), in 43% of Crohn's- associated carcinomas, and in 14% of dysplasias. Overexpression of p53 gene product and/or 17p allelic loss were present in 47% of sporadic carcinomas and 33% of contiguous adenomas and in 71% of Crohn's- associated carcinomas and 43% of dysplasias. In contrast, allelic losses of 5q (adenomatous polyposis coli [APC] gene region) and 18q (deleted in colorectal cancer [DCC] gene region) were rare. DNA replication errors (RERs) were present in 13% of sporadic carcinomas and in the carcinoma and dysplasias of 1 patient with Crohn's disease (14%), but mutations in the transforming growth factor beta type II receptor (TGFbeta RII) gene were absent.
CONCLUSIONS: Accumulation of ras and p53 alterations occurs during the adenoma/dysplasia-carcinoma sequence in small intestinal carcinogenesis, but a ras-independent pathway may also exist. The infrequent loss of the APC and DCC regions and the absence of TGFbeta RII gene mutation in RER-positive neoplasms contrast with colorectal carcinogenesis. (Gastroenterology 1997 Jul;113(1):127-35)