Detailed deletion mapping of loss of heterozygosity on 22q13 in sporadic colorectal cancer.
OBJECTIVE
Both development and progression of malignancies occur as a multistep process, requiring the activation of oncogenes and the inactivation of several tumor suppressor genes. The loss of heterozygosity (LOH) of tumor suppressor genes is believed to play a key role in carcinogenesis of colorectal cancer (CRC). In this study, we analyzed the LOH of seven loci on chromosome 22q13 in an effort to identify candidate tumor suppressor genes involved in colorectal carcinogenesis.


METHODS
Matched tumor and normal tissue DNA were analyzed by PCR using fluorescence-labeled polymorphic microsatellite markers in 83 CRC patients. PCR products were eletrophoresed and LOH was determined by calculating the peak height acquired through computer software. Comparisons between LOH frequency and clinicopathological features were performed by chi2 test. P<0.05 was considered as statistical significance.


RESULTS
The average LOH frequency of chromosome 22q13 was 28.38%. The highest LOH frequency was 64.71% on D22S1160 locus, and the lowest was 21.43% on D22S1141 locus. We detected two obvious minimal deletion regions: one between markers D22S1171 and D22S274, the other flanked by markers D22S1160 and D22S1149, each about 2.7 and 1.8 cm, respectively. None had lost in all informative loci. LOH frequency on D22S1171 is 50% on distal colon, which was higher than that on proximal one (P = 0.020); on D22S114 locus, none LOH event occurred in patients with liver metastasis, whilst 46.94% occurred in patients without liver metastasis (P = 0.008); on D22S1160 locus, LOH frequency in lymph nodes metastasis patients was 83.33%, which was much higher than 43.75% without lymph nodes metastasis ones (P = 0.016). There was no statistical significance between clinicopathological features and other loci.


CONCLUSIONS
This study provides evidence of two minimal deletion regions, which may harbor putative tumor suppressor genes related to progression and metastasis in sporadic colorectal carcinoma on chromosome 22q13.
Zheng
Hai-Tao
HT
Department of General Surgery, Shanghai First People Hospital, 85 Wujin Road, Shanghai 200080, China.
Peng
Zhi-Hai
ZH
Zhou
Chong-Zhi
CZ
Li
Da-Peng
DP
Wang
Zhao-Wen
ZW
Qiu
Guo-Qiang
GQ
He
Lin
L
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002874:Chromosome Mapping; D002892:Chromosomes, Human, Pair 22; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged