title: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Obstetrics-Gynecology, Weill Medical College of Cornell University, New York, NY 10021, USA. Arziman@lycosmail.com
authors.forename: Iordanis I
authors.initials: II
authors.lastname: Arzimanoglou
authors.forename: Lise Lotte
authors.initials: LL
authors.lastname: Hansen
authors.forename: David
authors.initials: D
authors.lastname: Chong
authors.forename: Zhen
authors.initials: Z
authors.lastname: Li
authors.forename: Maria C
authors.initials: MC
authors.lastname: Psaroudi
authors.forename: Constantine
authors.initials: C
authors.lastname: Dimitrakakis
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Jacovina
authors.forename: Maria
authors.initials: M
authors.lastname: Shevchuk
authors.forename: Linda
authors.initials: L
authors.lastname: Reid
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Hajjar
authors.forename: Stamatis
authors.initials: S
authors.lastname: Vassilaros
authors.forename: Stylianos
authors.initials: S
authors.lastname: Michalas
authors.forename: Fred
authors.initials: F
authors.lastname: Gilbert
authors.forename: Frank A
authors.initials: FA
authors.lastname: Chervenak
authors.forename: Hugh R K
authors.initials: HR
authors.lastname: Barber
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D001483:Base Sequence; D002352:Carrier Proteins; D004260:DNA Repair / Q000235:genetics; D004273:DNA, Neoplasm / Q000097:blood / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats / Q000235:genetics; D008969:Molecular Sequence Data; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D000070957:MutL Protein Homolog 1; D000074081:MutS Homolog 3 Protein; D009363:Neoplasm Proteins / Q000235:genetics*; D009687:Nuclear Proteins; D010051:Ovarian Neoplasms / Q000097:blood / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D000070957:MutL Protein Homolog 1; D000074081:MutS Homolog 3 Protein; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; C501486:MLH1 protein, human; C078444:MSH3 protein, human; C421109:multidrug resistance-associated protein 1