Genetic diagnosis strategy of hereditary non-polyposis colorectal cancer.
OBJECTIVE
To study the characteristics of mismatch repair gene mutation of Chinese hereditary non-polyposis colorectal cancer (HNPCC) and hMLH1 gene promoter methylation, and to improve the screening strategy and explore the pertinent test methods.


METHODS
A systematic analysis of 30 probands from HNPCC families in the north of China was performed by immunohistochemistry, microsatellite instability (MSI), gene mutation and methylation detection.


RESULTS
High frequency microsatellite instability occurred in 25 probands (83.3%) of HNPCC family. Loss of hMLH1 and hMSH2 protein expression accounted for 88% of all microsatellite instability. Pathogenic mutation occurred in 14 samples and 3 novel mutational sites were discovered. Deletion of exons 1-6, 1-7 and 8 of hMSH2 was detected in 3 samples and no large fragment deletion was found in hMLH1. Of the 30 probands, hMLH1 gene promoter methylation occurred in 3 probands. The rate of gene micromutation detection combined with large fragment deletion detection was 46.7%-56.7%. The rate of the two methods in combination with methylation detection was 63.3%.


CONCLUSIONS
Scientific and rational detection strategy can improve the detection rate of HNPCC. Based on traditional molecular genetics and combined with epigenetics, multiple detection methods can accurately diagnose HNPCC.
Sheng
Jian-Qiu
JQ
Department of Gastroenterology, General Hospital of Beijing Military Command, Dongcheng District, Beijing, China. jianqiu@263.net
Zhang
Hong
H
Ji
Min
M
Fu
Lei
L
Mu
Hong
H
Zhang
Ming-Zhi
MZ
Huang
Ji-Sheng
JS
Han
Min
M
Li
Ai-Qin
AQ
Wei
Zhi
Z
Sun
Zi-Qin
ZQ
Wu
Zi-Tao
ZT
Xia
Chang-Hong
CH
Li
Shi-Rong
SR
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000175:diagnosis / Q000235:genetics*; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D053843:DNA Mismatch Repair; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D005091:Exons; D018095:Germ-Line Mutation; D006801:Humans; D053842:Microsatellite Instability; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D017384:Sequence Deletion
D048868:Adaptor Proteins, Signal Transducing; D004273:DNA, Neoplasm; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D004247:DNA; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein