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      • SCOPUSKCI등재

        유전학적 불안전성을 보이는 대장암의 발생기전

        김효종(Hyo Jong Kim),김윤화(Youn Hwa Kim),정혜전(Heo Jeon Cheong),동석호(Seok Ho Dong),김배영(Bae Young Kim),김병호(Byung Ho Kim),이정일(Joung Il Lee),장영운(Young Woon Chang),장린(Rin Chang),양문호(Moon Ho Yang) 대한소화기학회 1996 대한소화기학회지 Vol.28 No.1

        N/A Background/Aims: Multiple genetic alterations in tumor suppressor genes(APC, MCC, DCC, p53) and oncogenes(K-ras) have been implicated in the development of colorectal carcinomas(CRCs). Recently, mutator genes(hMSH2, hMLH1, hPMS1, hPMS2), which are characterized by the development of particular form of genetic instability, termed RER(replication error) was reported in CRCs. It is postulated that RER may be required for multiple genetic alterations in the development of CRCs. But the mode of genetic alterations caused by RER is not certain. To evaluate the mode of genetic alterations caused by RER in multistage carcinogeneis, we compared the frequency of p53 expression, known to be involved in the pathogenesis of CRC, in two groups of tumors. RER(+); those demonstrating RER, and RER( ); those lacking such genetic alterations. Methods: RER test at microsatellite loci; DNA was extracted from normal and tumor tissues using cryostat sectioning method. Purified DNA was subjected to a PCR-based technique in which(CA)n repeat sequence were amplified and RERs were detected when a change in allele length was detected. Immunohistochemical analysis of p53 expression; Deparaffinized section of formalin-fixed tumor tissue samples were immunostained for p53 protein, using a monoclonal p53-specific DO7 antibody. Results: The frequency of RER in sporadic CRC was 40.1%(9/22). P53 expression was observed in 6 of 18 carcinoma(33.3%). The frequency of p53 immunostaining was lower in tumors demonstrating RER(25% vs. 40%). All tumor demonstrating RER at multiple loci did not exhibited p53 immunostaining. Conclusions: These results suggest that RER is likely to play an important role in the pathogenesis of CRCs probably by the different mode of genentic alterations from those lacking RER. (Korean J Gastroenterol 1996;28: 36-46)

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