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

Gastroenterology. 1997 Jul;113(1):127-35. 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenocarcinoma / complications
  • Adenocarcinoma / genetics*
  • Adenoma / complications
  • Adenoma / genetics*
  • Adult
  • Aged
  • Chromosome Deletion*
  • Chromosomes, Human, Pair 17
  • Chromosomes, Human, Pair 18
  • Chromosomes, Human, Pair 5
  • Colorectal Neoplasms / genetics
  • Crohn Disease / complications
  • Crohn Disease / genetics*
  • Female
  • Genes, p53 / genetics*
  • Genes, ras / genetics*
  • Humans
  • Intestinal Neoplasms / complications
  • Intestinal Neoplasms / genetics*
  • Male
  • Middle Aged
  • Point Mutation*
  • Polymerase Chain Reaction