[Refined deletion mapping of loss of heterozygosity on 22q13 in sporadic colorectal carcinoma].
OBJECTIVE
To screen the candidate TSGs on 22q13 involved in sporadic colorectal cancer.


METHODS
The DNA samples of 83 cases with colorectal carcinoma and normal tissues were analyzed using eight fluorescent labeled polymorphic microsatellite markers by PCR. PCR products were electrophoresed on an ABI 377 DNA sequencer. Genescan 3.7 and Genotype 3.7 software was used for LOH scanning and analysis. Comparison between LOH frequency and clinicopathological factors were performed by chia2 test.


RESULTS
The prevalence of LOH was 35.58%, and the average hereditary distance was 1.9 cM. The highest frequency of LOH (D22S1160 locus) and the lowest (D22S1170 locus) were 64.71% and 20%, respectively. Two obvious LOH regions were detected: One between D22S1171 locus and D22S274 locus (about 2.7 cM); another between D22S1160 and D22S1149 locus (about 1.8 cM). Furthermore,significant differences were observed between the frequency of LOH on D22S1171 locus and tumors location (P=0.020), the frequency of LOH on D22S114 locus and liver metastasis (P=0.008), the frequency of LOH on D22S1160 locus and lymph node metastasis (P=0.016). No significant differences were found between LOH on other loci and those factors above. Gene function screening revealed that ARHGAP8 and PPARA gene were involved in carcinogenesis.


CONCLUSIONS
Two obvious high frequency LOH regions are detected by refined deletion mapping. One locates between D22S1171 locus and D22S274 locus (about 2.7 cM); another locates between D22S1160 and D22S1149 locus (about 1.8cM), ARHGAP8 and PPARA gene may be TSGs which contribute to carcinogenesis and progression of sporadic CRC on 22q13 region.
Department of General Surgery, Shanghai First Peoples Hospital, Shanghai Jiaotong University, Shanghai 200080, China.
Hai-tao
HT
Zheng
Hua-mei
HM
Tang
Zhi-hai
ZH
Peng
Chong-zhi
CZ
Zhou
Lin
L
He
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002892:Chromosomes, Human, Pair 22; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D017384:Sequence Deletion