遗传性非息肉病性结直肠癌（HNPCC）家族患者微卫星标记的遗传分析。

Genetic analysis of microsatellite markers in patients from hereditary nonpolyposis colorectal cancer (HNPCC) families.

作者信息

Smolarz Beata, Romanowicz-Makowska Hanna, Langner Ewa, Kozlowska Elzbieta, Kulig Andrzej, Dziki Adam

机构信息

Laboratory of Molecular Genetics, Department of Pathology, Institute of Polish Mother's Memorial Hospital, Lodz, Poland.

出版信息

Exp Oncol. 2004 Sep;26(3):205-9.

PMID:15494688

Abstract

AIM

Microsatellite instability (MSI) is due to defective DNA mismatch repair (MMR) and is characteristic of hereditary nonpolyposis colorectal cancer (HNPCC) tumors. The role of MSI in familial predisposition to colorectal cancer was investigated in this study by both microsatellite analysis and mutation screening of the two major MMR genes MLH1 and MSH2 among familial cases.

METHODS

PCR-based microsatellite analysis was performed in blood obtained from 30 members from HNPCC families. Blood samples age matched healthy individuals (n = 28) served as control. MSI was studied at five loci containing single- or dinucleotide repeat sequences and mapping to different chromosomal locations: BAT-25 (at locus 4q12), BAT-26 (2p16), D2S123 (2p16-p21), D5S346 (5q21-q22) and D17S250 (17q11.2-q12).

RESULTS

MSI frequency was higher in member of HNPCC families [7/30 (23%)] than in control [3/28 (10.7%)] cases. Two MLH1 and one MSH2 mutations were identified in 7 MSI positive samples from HNPCC families. MLH1/MSH2 mutations were only in MSI high samples detected.

CONCLUSION

Genetic alterations seem to be a risk factor of colorectal cancer in subjects belonged to HNPCC families with high incidence of this cancer.

摘要

目的

微卫星不稳定性（MSI）是由于DNA错配修复（MMR）缺陷所致，是遗传性非息肉病性结直肠癌（HNPCC）肿瘤的特征。本研究通过微卫星分析以及对家族性病例中两个主要MMR基因MLH1和MSH2进行突变筛查，探讨了MSI在结直肠癌家族易感性中的作用。

方法

对来自HNPCC家族的30名成员的血液进行基于聚合酶链反应（PCR）的微卫星分析。年龄匹配的健康个体（n = 28）的血液样本作为对照。在五个含有单核苷酸或二核苷酸重复序列且定位于不同染色体位置的位点研究MSI：BAT-25（位于4q12位点）、BAT-26（2p16）、D2S123（2p16-p21）、D5S346（5q21-q22）和D17S250（17q11.2-q12）。