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World J Gastroenterol. Jan 7, 2008; 14(1): 90-94
Published online Jan 7, 2008. doi: 10.3748/wjg.14.90
Are there tumor suppressor genes on chromosome 4p in sporadic colorectal carcinoma?
Hai-Tao Zheng, Li-Xin Jiang, Zhong-Chuan Lv, Da-Peng Li, Chong-Zhi Zhou, Jian-Jun Gao, Lin He, Zhi-Hai Peng
Hai-Tao Zheng, Li-Xin Jiang, Zhong-Chuan Lv, Department of Abdominal Surgery, The Affiliated Yantai Yuhuangding Hospital of Qingdao University Medical College, Yantai 264000, Shangdong Province, China
Zhi-Hai Peng, Da-Peng Li, Chong-Zhi Zhou, Department of General Surgery, The Affiliated Shanghai First People’s Hospital of Shanghai Jiaotong University, Shanghai 200080, China
Jian-Jun Gao, Lin He, Shanghai Bio-X Center, Shanghai Jiaotong University, Shanghai 200031, China
Correspondence to: Dr. Zhi-Hai Peng, Department of General Surgery, The Affiliated Shanghai First People’s Hospital of Shanghai Jiaotong University, Shanghai 200080, China. pengzh@hotmail.com
Telephone: +86-21-63250090-4312
Received: April 11, 2007
Revised: September 24, 2007
Published online: January 7, 2008
Abstract

AIM: 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 eletrophoresed 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 χ2 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.

CONCLUSION: 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).

Keywords: Loss of heterozygosity; Colorectal carcinoma; Chromosome 4p; Tumor suppressor gene