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Title
Genetic Instability and Mutations of Mismatch Repair (MMR) and p53 Gene in Colorectal Cancers with Multiple Polyps and Sporadic Colorectal Cancers
Author
Sung Won Chun, Suk Kyun Chang
Place of duty
Publicationinfo
Journal of Korean Soc Coloproctol 2002 | Vol.18 No.6 | 353 ~ 363, 11 pages
Keyword
»ê¹ß¼º ´ëÀå-Á÷Àå¾Ï; ´Ù¹ß¼º ¿ëÁ¾¼º ´ëÀå-Á÷Àå¾Ï; À¯ÀüÀû ºÒ¾ÈÁ¤¼º; p53 À¯ÀüÀÚ; Sporadic colorectal cancer; Colorectal cancer with multiple polyps; Genetic instability; p53 gene;
Abstract
Purpose:
General conceptions of carcinogenic mechanisms by recent reports are ras-p53 gene pathway in sporadic colorectal cancers (SCC), MMR gene pathway in hereditary nonpolyposis colorectal cancer (HNPCC) and APC gene in familial
adenomatous
polyposis (FAP). But in the colorectal cancer with multiple polyps (CCMP), the carcinogenic pathway is not still defined exactly. In order to find out the which carcinogenic pathway control the CCMP and SCC, genetic instability were studied in CCMP
and
SCC.
Methods:
In this study, genetic instability on D2S123, D3S1029, D5S107, D6S87 and AP¥Ä3 foci and gene mutations of hMLH
1
(exon 2, 16, 19), hMSH
2
(exon 11, 12, 13, 14) gene of MMR gene, p53 gene (exon 5, 6, 7, 8, 9)
were
studied on the 60 DNA samples of CCMP (30 cases) and SCC (30 cases).
Results:
1. Observed positive genetic instability was higher in CCMP (30%) than SCC (20%), and was higher in right colon cancers (33%) than left colon cancers (23%) or rectal cancers (17%), but not significant statisitically. And observed
positive genetic instability was lower in moderate differentiated cancers (16%) than well (67%) or poorly (60%) differentiated cancers (P=0.005). 2. Any mutations of hMLH
1
and hMSH
2
gene of MMR gene were not observed in both
of
CCMP and SCC, but 3 cases (2 CCMPs and 1 SCC) point mutations of intron of hMSH
2
gene, which were higher in positive genetic instability than negative (P=0.002). 3. This 3 cases point mutations were C for T which were on 6th bases
upstream
from codon 669. 4. From the results of SSCP for nucleotide sequencing of p53 gene, the abnormal bands were observed in 30% (9 of 30) of CCMP and SCC. Also the abnormal bands were observed in both of positive or negative genetic instability
without
differences.
Conclusions:
With above results the authors suggested that the mechanism of genetic instability and mutations of p53 gene strongly affect the mechanism of carcinogenesis in SCC and CCMP. And there are relationship between genetic instability
and
point mutation at intron region of hMSH
2
gene. However further evaluation and research is needed to establish relation between APC gene and other different kind of MMR gene.
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´ëÇÑ´ëÀåÇ×¹®ÇÐȸÁö 2002 | 18±Ç 6È£ 353 ~ 363, 11 pages
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»ê¹ß¼º ´ëÀå-Á÷Àå¾Ï; ´Ù¹ß¼º ¿ëÁ¾¼º ´ëÀå-Á÷Àå¾Ï; À¯ÀüÀû ºÒ¾ÈÁ¤¼º; p53 À¯ÀüÀÚ; Sporadic colorectal cancer; Colorectal cancer with multiple polyps; Genetic instability; p53 gene;