RER and LOH association with sporadic colorectal cancer in Taiwanese patients.
OBJECTIVE
This association study was undertaken to determine replication error and loss of heterozygosity in colorectal tumors using a set of 10 microsatellite markers linked to APC, hMSH2, hMLH1, DCC, P53, NM23, HPC1 and MET genes as well as tumor suppressor genes on 8p22.


METHODS
Thirty-nine patients diagnosed and confirmed with sporadic colorectal cancer were biopsied. Their stored frozen tissues were subsequently retrieved for simultaneous analyses of replication error and loss of heterozygosity via an automated fluorescent microsatellite assay.


RESULTS
Replication error was observed in 8/39 of the cases (20.5%) and had significantly higher frequency in the patients younger than 60 yr (P = 0.049). More than one third of informative tumors showed loss of heterozygosity at P53, DCC and APC genes (57.9%, 35.3% and 33.3%, respectively). Loss of heterozygosity at TP53-Dint marker was significantly associated with survival status (P = 0.038) in which a higher frequency was observed in the patients who died from colorectal cancer. Of 22 informative tumors, 6 (27.3%) showed loss of heterozygosity at the D8S254 marker that is suspected to be near one or more tumor suppressor genes and was significantly associated with gender (P = 0.046). All 6 cases of loss of heterozygosity at D8S254 were found in male patients. The frequencies of loss of heterozygosity at the NM23, hMSH2, hMLH1 and HPC1 genes were 18.5%, 12.1%, 9.1% and 7.4%, respectively. None of the cases examined displayed loss of heterozygosity at the MET oncogene.


CONCLUSIONS
Additional microsatellite markers other than those associated with colorectal cancer were used to conduct the study of genomic instability and alterations in colorectal cancer tumors. The present results for the sporadic occurrence of colorectal cancer in Taiwanese patients further extend the correlation of clinical pathology and prognosis with the analysis of replication error and loss of heterozygosity.
Tsai
Ming-Hong
MH
Division of Colon and Rectal Surgery, Cardinal Tien Hospital, Taipei, Taiwan, ROC.
Yang
Ya-Chien
YC
Chen
Kuang-Ho
KH
Jiang
Jeng-Kae
JK
Chou
Shao-Jiun
SJ
Chiang
Tai-Chow
TC
Jan
Hsiang-Shan
HS
Lou
Mary Ann
MA
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D004261:DNA Replication / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D016147:Genes, Tumor Suppressor / Q000502:physiology; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D009367:Neoplasm Staging; D013624:Taiwan
D004273:DNA, Neoplasm