Genetic characterization of colorectal cancers in young patients based on chromosomal loss and microsatellite instability.
BACKGROUND
In recent studies a high frequency of microsatellite instability among colorectal cancers in young patients has been reported, but the frequency of microsatellite instability (MSI) and chromosomal instability among colorectal cancers in young patients has not yet been fully elucidated. Only one report showed an increased loss of heterozygosity (LOH) ratio at 9p locus, which harbors tumor suppressor genes p16. The LOH and MSI status among colorectal cancers in young patients was examined.


METHODS
Twenty-five patients under 40 years of age diagnosed with colorectal cancer were examined for MSI and LOH using 17 microsatellite markers, and also p16 expression patterns were evaluated by immunohistochemistry and methylation status of the p16 gene was assessed by methylation-specific PCR.


RESULTS
MSI was observed in only one case (4%). LOH at 2p, 5q, 9p, 11q, 17p, and 18q was observed in 41%, 59%, 42%, 35%, 46%, and 56% of cases, respectively. Eighty-three percent of patients showed p16-positive expression patterns. Fifty percent of colorectal cancers in young patients exhibited p16 methylation (3/6).


CONCLUSIONS
Our study demonstrated that colorectal cancers in young patients without MSI showed a high frequency of LOH at the 9p locus. However, LOH status at 9p and p16 expression pattern did not show a significant correlation. Other tumor suppressor genes on the 9p, with the exception of p16, may play an important role in the carcinogenesis of colorectal cancers in young patients.
Tada
T
T
Department of Surgical Oncology, Graduate School of Medicine, University of Tokyo, Tokyo 113-8655, Japan. tadat-sur@h.u-tokyo.ac.jp
Watanabe
T
T
Kanazawa
T
T
Kazama
S
S
Koketsu
S
S
Nagawa
H
H
D000230:Adenocarcinoma / Q000235:genetics*; D000328:Adult; D015179:Colorectal Neoplasms / Q000235:genetics*; D019175:DNA Methylation; D005260:Female; D015870:Gene Expression; D019942:Genes, p16; D006801:Humans; D007150:Immunohistochemistry; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D016133:Polymerase Chain Reaction