Molecular genetic profiles of colitis-associated neoplasms.
OBJECTIVE
A major long-term risk for patients with chronic idiopathic colitis is the development of colorectal dysplasia and adenocarcinoma. The presence or absence of specific genetic changes in these lesions will provide important insights into the relationship of colitis-associated dysplasia and the development of carcinoma.


METHODS
A case-study approach was used to develop detailed molecular genetic profiles of advanced dysplasias and carcinomas from six patients with ulcerative colitis or Crohn's colitis.


RESULTS
Numerous genetic alterations were identified in each of the dysplasias and carcinomas profiled. These genetic alterations involved many of the same targets found in sporadic colorectal tumors and included multiple sites of allelic deletion, microsatellite instabilities, and mutations of the K-ras, p53, and APC genes. The progression of dysplasia to carcinoma was often accompanied by an accumulation of these mutations.


CONCLUSIONS
Genetic alterations are common in colitis-associated neoplasia, just as in sporadic colorectal neoplasia. This could have important implications for the evaluation and treatment of patients with colitis.
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
S E
SE
Kern
M
M
Redston
A B
AB
Seymour
C
C
Caldas
S M
SM
Powell
S
S
Kornacki
K W
KW
Kinzler
D000230:Adenocarcinoma / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000368:Aged; D000483:Alleles; D003092:Colitis / Q000150:complications*; D003106:Colon / Q000378:metabolism / Q000473:pathology; D015179:Colorectal Neoplasms / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D017491:Genes, APC / Q000235:genetics; D016158:Genes, p53 / Q000235:genetics; D011905:Genes, ras / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009154:Mutation; D016160:Retinoblastoma Protein / Q000378:metabolism
D016160:Retinoblastoma Protein