Genetic alterations in sporadic and Crohn's-associated adenocarcinomas of the small intestine.
OBJECTIVE
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.
Rashid
A
A
Department of Pathology and Oncology Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2196, USA.
Hamilton
S R
SR
D000230:Adenocarcinoma / Q000150:complications / Q000235:genetics*; D000236:Adenoma / Q000150:complications / Q000235:genetics*; D000328:Adult; D000368:Aged; D002872:Chromosome Deletion; D002886:Chromosomes, Human, Pair 17; D002887:Chromosomes, Human, Pair 18; D002895:Chromosomes, Human, Pair 5; D015179:Colorectal Neoplasms / Q000235:genetics; D003424:Crohn Disease / Q000150:complications / Q000235:genetics*; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D007414:Intestinal Neoplasms / Q000150:complications / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D016133:Polymerase Chain Reaction