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

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:1) 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.

journal_name

Anticancer Res

journal_title

Anticancer research

authors

Arzimanoglou II,Hansen LL,Chong D,Li Z,Psaroudi MC,Dimitrakakis C,Jacovina AT,Shevchuk M,Reid L,Hajjar KA,Vassilaros S,Michalas S,Gilbert F,Chervenak FA,Barber HR

subject

Has Abstract

pub_date

2002-03-01 00:00:00

pages

969-75

issue

2A

eissn

0250-7005

issn

1791-7530

journal_volume

22

pub_type

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