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Mutation analysis of FANCD2, BRIP1/BACH1, LMO4 and SFN in familial breast cancer.
- Source :
-
Breast cancer research : BCR [Breast Cancer Res] 2005; Vol. 7 (6), pp. R1005-16. Date of Electronic Publication: 2005 Oct 21. - Publication Year :
- 2005
-
Abstract
- Introduction: Mutations in known predisposition genes account for only about a third of all multiple-case breast cancer families. We hypothesized that germline mutations in FANCD2, BRIP1/BACH1, LMO4 and SFN may account for some of the unexplained multiple-case breast cancer families.<br />Methods: The families used in this study were ascertained through the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer (kConFab). Denaturing high performance liquid chromatography (DHPLC) analysis of the coding regions of these four genes was conducted in the youngest affected cases of 30 to 267 non-BRCA1/2 breast cancer families. In addition, a further 399 index cases were also screened for mutations in two functionally significant regions of the FANCD2 gene and 253 index cases were screened for two previously reported mutations in BACH1 (p. P47A and p. M299I).<br />Results: DHPLC analysis of FANCD2 identified six silent exonic variants, and a large number of intronic variants, which tagged two common haplotypes. One protein truncating variant was found in BRIP1/BACH1, as well as four missense variants, a silent change and a variant in the 3' untranslated region. No missense or splice site mutations were found in LMO4 or SFN. Analysis of the missense, silent and frameshift variants of FANCD2 and BACH1 in relatives of the index cases, and in a panel of controls, found no evidence suggestive of pathogenicity.<br />Conclusion: There is no evidence that highly penetrant exonic or splice site mutations in FANCD2, BRIP1/BACH1, LMO4 or SFN contribute to familial breast cancer. Large scale association studies will be necessary to determine whether any of the polymorphisms or haplotypes identified in these genes contributes to breast cancer risk.
- Subjects :
- 14-3-3 Proteins
Adaptor Proteins, Signal Transducing
Adult
Age of Onset
Aged
Alternative Splicing
Biomarkers, Tumor genetics
DNA Mutational Analysis
DNA-Binding Proteins genetics
Exonucleases genetics
Exoribonucleases
Fanconi Anemia Complementation Group D2 Protein genetics
Fanconi Anemia Complementation Group Proteins
Female
Germ-Line Mutation
Homeodomain Proteins genetics
Humans
LIM Domain Proteins
Middle Aged
Neoplasm Proteins genetics
Pedigree
RNA Helicases genetics
Risk Factors
Transcription Factors genetics
Breast Neoplasms genetics
Genetic Predisposition to Disease
Subjects
Details
- Language :
- English
- ISSN :
- 1465-542X
- Volume :
- 7
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Breast cancer research : BCR
- Publication Type :
- Academic Journal
- Accession number :
- 16280053
- Full Text :
- https://doi.org/10.1186/bcr1336