人错配修复蛋白1（hMLH1）频繁发生杂合性缺失、人错配修复蛋白3（hMSH3）中一个高度可变的单核苷酸多态性以及卵巢癌中可忽略不计的编码不稳定性。

Frequent LOH at hMLH1, a highly variable SNP in hMSH3, and negligible coding instability in ovarian cancer.

作者信息

Arzimanoglou Iordanis I, Hansen Lise Lotte, Chong David, Li Zhen, Psaroudi Maria C, Dimitrakakis Constantine, Jacovina Andrew T, Shevchuk Maria, Reid Linda, Hajjar Katherine A, Vassilaros Stamatis, Michalas Stylianos, Gilbert Fred, Chervenak Frank A, Barber Hugh R K

机构信息

Department of Obstetrics-Gynecology, Weill Medical College of Cornell University, New York, NY 10021, USA.

出版信息

Anticancer Res. 2002 Mar-Apr;22(2A):969-75.

PMID:12014680

Abstract

BACKGROUND

Molecular alterations such as DNA microsatellite instability (MSI/RER), single nucleotide polymorphism (SNP) and loss of heterozygosity (LOH) can occur throughout the genome and be associated with different types of cancer. In the present study, we aimed at detecting molecular alterations within the mismatch DNA repair genes in ovarian cancer (OC), using a sensitive, accurate and reliable protocol we have developed.

MATERIALS AND METHODS

A combination of high-resolution GeneScan software analysis and automated DNA cycle sequencing was used.

RESULTS

Negligible coding MSI was observed in selected sequences of mismatch DNA repair genes in our series of sixty-two ovarian tumors and matched blood DNAs. Unlike MSI, loss of one hMLH1 allele was scored in almost half (47%) of the informative cases. In addition, an SNP in hMSH3/intron 5 was found to be highly variable in OC patients.

CONCLUSION

Coding DNA instability is likely to be a very rare event in OC and, therefore, may not significantly contribute to the development of OC, and 2) the high frequency of LOH at hMLH1 observed in our ovarian tumors suggests that further investigation is needed to determine if such a trend exists in other mismatch DNA repair and/or critical genes.

摘要