Are there tumor suppressor genes on chromosome 4p in sporadic colorectal carcinoma?
OBJECTIVE
To study the candidate tumor suppressor genes (TSG) on chromosome 4p by detecting the high frequency of loss of heterozygosity (LOH) in sporadic colorectal carcinoma in Chinese patients.


METHODS
Seven fluorescent labeled polymorphic microsatellite markers were analyzed in 83 cases of colorectal carcinoma and matched normal tissue DNA by PCR. PCR products were electrophoresed on an ABI 377 DNA sequencer. Genescan 3.7 and Genotype 3.7 software were used for LOH scanning and analysis. The same procedure was performed by the other six microsatellite markers spanning D4S3013 locus to make further detailed deletion mapping. Comparison between LOH frequency and clinicopathological factors was performed by c2 test.


RESULTS
Data were collected from all informative loci. The average LOH frequency on 4p was 24.25%, and 42.3% and 35.62% on D4S405 and D4S3013 locus, respectively. Adjacent markers of D4S3013 displayed a low LOH frequency (< 30%) by detailed deletion mapping. Significant opposite difference was observed between LOH frequency and tumor diameter on D4S412 and D4S1546 locus (0% vs 16.67%, P = 0.041; 54.55% vs 11.11%, P = 0.034, respectively). On D4S403 locus, LOH was significantly associated with tumor gross pattern (11.11%, 0, 33.33%, P = 0.030). No relationship was detected on other loci compared with clinicopathological features.


CONCLUSIONS
By deletion mapping, two obvious high frequency LOH regions spanning D4S3013 (4p15.2) and D4S405 (4p14) locus are detected. Candidate TSG, which is involved in carcinogenesis and progression of sporadic colorectal carcinoma on chromosome 4p, may be located between D4S3017 and D4S2933 (about 1.7 cm).
Zheng
Hai-Tao
HT
Department of Abdominal Surgery, The Affiliated Yantai Yuhuangding Hospital of Quingdao University Medical College, Yantai 264000, Shangdon Province, China.
Jiang
Li-Xin
LX
Lv
Zhong-Chuan
ZC
Li
Da-Peng
DP
Zhou
Chong-Zhi
CZ
Gao
Jian-Jun
JJ
He
Lin
L
Peng
Zhi-Hai
ZH
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics*; D002894:Chromosomes, Human, Pair 4; D015179:Colorectal Neoplasms / Q000235:genetics*; D016147:Genes, Tumor Suppressor; D005819:Genetic Markers; D006801:Humans; D019656:Loss of Heterozygosity; D008875:Middle Aged
D005819:Genetic Markers