title: Mutational analysis of the BRCA1 tumor suppressor gene in endometrial carcinoma.
abstract: OBJECTIVE
  To investigate whether alteration of BRCA1 tumor suppressor gene occurs in sporadic endometrial carcinomas.
  
  
  METHODS
  Genomic DNAs were prepared from 33 consecutively collected endometrial carcinoma tissues for BRCA1 mutational analysis. To screen for BRCA1 mutation, polymerase chain reaction (PCR) amplification and single strand conformation polymorphism (SSCP) technique were used with 41 overlapping PCR primer pairs for the 23 coding exons of BRCA1. Tumors that demonstrated SSCP variants were further subjected to direct DNA sequencing in the appropriate exons to identify the DNA alteration.
  
  
  RESULTS
  In addition to detecting a previously described polymorphism in exon 11, single strand conformation polymorphism analysis of the 33 endometrial cancers identified 3 tumors with mobility shifts. Two tumors shifted in exon 3 and showed the same pattern of band shift. The other tumor shifted in exon 9. DNA sequencing revealed sequence alterations in the 3 tumors; all appeared heterozygous. In the 2 tumors shifted in exon 3, the sequence alteration caused no amino acid change and was consistent with an infrequent silent polymorphism. In the third tumor, a missense alteration at codon 191 was detected and was recognized as germline in origin.
  
  
  CONCLUSIONS
  Because a normal allele of BRCA1 was retained in the tumor where a germline missense alteration was detected, the heterozygous DNA alteration should not be cancer predisposing in terms of the two-hit model for inactivation of the tumor suppressor gene. We conclude that mutation of BRCA1 may not be involved in the development of sporadic endometrial cancer.
authors.affiliation: Department of Obstetrics and Gynecology, Taichung Veterans General Hospital, Taichung, Taiwan.
authors.forename: F S
authors.initials: FS
authors.lastname: Liu
authors.forename: E S
authors.initials: ES
authors.lastname: Ho
authors.forename: R T
authors.initials: RT
authors.lastname: Shih
authors.forename: A
authors.initials: A
authors.lastname: Shih
mesh_terms: D004252:DNA Mutational Analysis; D017931:DNA Primers; D004273:DNA, Neoplasm / Q000235:genetics*; D016889:Endometrial Neoplasms / Q000235:genetics*; D005260:Female; D019398:Genes, BRCA1 / Q000235:genetics*; D006801:Humans; D009154:Mutation; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational
chemical_list: D017931:DNA Primers; D004273:DNA, Neoplasm