Loss of heterozygosity on long arm of chromosome 22 in sporadic colorectal carcinoma.
OBJECTIVE
The loss of heterozygosity (LOH) on tumor suppressor genes is believed to play a key role in carcinogenesis of colorectal cancer. In this study, we analyzed the LOH at 5 loci on the long arm of chromosome 22 in sporadic colorectal cancer to identify additional loci involved in colorectal tumorigenesis.


METHODS
Five polymorphic microsatellite markers were analyzed in 83 cases of colorectal and normal DNA by PCR. PCR products were eletrophoresed on an ABI 377 DNA sequencer; Genescan 3.1 and Genotype 2.1 software were used for LOH scanning and analysis. Comparison between LOH frequency and clinicopathological data were performed by chi(2) test. P<0.05 was considered as statistically significant.


RESULTS
The average LOH frequency on chromosome 22q was 28.38 %. The region between markers D22S280 and D22S274 (22q12.2-q13.33) exhibited relatively high LOH frequency. The two highest LOH loci with frequencies of 35.09 % and 34.04 % was identified on D22S280 (22q12.2-12.3) and D22S274 (22q13.32-13.33). 8 cases showed LOH at all informative loci, suggesting that one chromosome 22q had been completely lost. On D22S274 locus, LOH frequency of rectal cancer was 50 % (9/18), which was higher than that of proximal colon cancer (12 %, 2/17) (P=0.018). The frequency of distal colon cancer was 42 % (5/12), also higher than that of proximal colon cancer. But there was no statistical significance. Putting both the tumors in distal colon and rectum together into consideration, the frequency, 47 % (14/30), was higher than that of proximal colon cancer (P=0.015),suggesting the mechanism of carcinogenisis was different in both groups.


CONCLUSIONS
This study provided evidence for the involvement of putative tumor suppressor genes related to the sporadic colorectal carcinoma on chromosome 22q. The tumor-suppressor-gene(s) might locate on the 22q12.2-12.3 and/or 22q13.32-13.33.
Zhou
Chong-Zhi
CZ
Department of General Surgery, Shanghai First People Hospital, 85 Wujin Road, Shanghai 200080, China.
Peng
Zhi-Hai
ZH
Zhang
Fang
F
Qiu
Guo-Qiang
GQ
He
Lin
L
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics*; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged