title: No evidence of involvement of germline BACH1 mutations in Finnish breast and ovarian cancer families.
abstract: Recently BACH1, a novel putative DNA helicase mapping to chromosome 17q22, was reported to interact specifically with BRCA1, and was suggested to be a candidate gene for predisposition to breast and ovarian cancers. Here, we screened 214 breast and ovarian cancer patients from 151 Finnish families for germline BACH1 mutations by utilising conformation-sensitive gel electrophoresis (CSGE) and genomic sequencing analysis. Four sequence alterations were observed in the exon regions of BACH1, three of which have been previously reported and were classified as polymorphisms. In 1 patient, a novel heterozygous 3101C>T variant was observed resulting in a proline to leucine substitution at codon 1034 (Pro1034Leu). This amino acid change occurs in the BRCA1 binding domain of the BACH1 protein. Although the 3101C>T transition was also found in one of the 304 control individuals with an unknown cancer status, it still remains possible that this alteration could represent a rare disease-related allele in the population. Functional assays are needed to resolve the biological significance of this novel BACH1 missense variant. Altogether, the available data suggest that germline mutations in BACH1 are extremely rare.
authors.affiliation: Department of Clinical Genetics, Oulu University Hospital/University of Oulu, PO Box 24, FIN-90029 OYS, Finland.
authors.forename: S-M
authors.initials: SM
authors.lastname: Karppinen
authors.forename: J
authors.initials: J
authors.lastname: Vuosku
authors.forename: K
authors.initials: K
authors.lastname: Heikkinen
authors.forename: M
authors.initials: M
authors.lastname: Allinen
authors.forename: R
authors.initials: R
authors.lastname: Winqvist
mesh_terms: D050976:Basic-Leucine Zipper Transcription Factors; D001943:Breast Neoplasms / Q000235:genetics*; D004273:DNA, Neoplasm / Q000032:analysis; D004591:Electrophoresis, Polyacrylamide Gel; D051856:Fanconi Anemia Complementation Group Proteins; D005260:Female; D005387:Finland; D005820:Genetic Testing; D006579:Heterozygote; D006801:Humans; D020125:Mutation, Missense / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics*; D010375:Pedigree; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C102108:BACH1 protein, human; D050976:Basic-Leucine Zipper Transcription Factors; D004273:DNA, Neoplasm; D051856:Fanconi Anemia Complementation Group Proteins; D014157:Transcription Factors