Mutation analysis of FANCD2, BRIP1/BACH1, LMO4 and SFN in familial breast cancer

File Description SizeFormat 
Mutation analysis of FANCD2, BRIP1/BACH1, LMO4 and SFN in familial breast cancer.pdfPublished version188.5 kBAdobe PDFView/Open
Title: Mutation analysis of FANCD2, BRIP1/BACH1, LMO4 and SFN in familial breast cancer
Authors: Lewis, AG
Flanagan, J
Marsh, A
Pupo, GM
Mann, G
Spurdle, AB
Lindeman, GJ
Visvader, JE
Brown, MA
Chenevix-Trench, G
Item Type: Journal Article
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. 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). 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. 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.
Issue Date: 21-Oct-2005
Date of Acceptance: 26-Sep-2005
URI: http://hdl.handle.net/10044/1/40822
DOI: http://dx.doi.org/10.1186/bcr1336
ISSN: 1465-542X
Publisher: BioMed Central
Start Page: R1005
End Page: R1016
Journal / Book Title: Breast Cancer Research
Volume: 7
Issue: 6
Copyright Statement: This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: Science & Technology
Life Sciences & Biomedicine
Oncology
ONCOLOGY
ANEMIA-BRCA PATHWAY
FANCONI-ANEMIA
LINKAGE ANALYSIS
OVARIAN-TUMORS
ALLELIC LOSS
GENE
PROTEIN
DOMAIN
CELLS
HYPERMETHYLATION
14-3-3 Proteins
Adaptor Proteins, Signal Transducing
Adult
Age of Onset
Aged
Alternative Splicing
Biomarkers, Tumor
Breast Neoplasms
DNA Mutational Analysis
DNA-Binding Proteins
Exonucleases
Exoribonucleases
Fanconi Anemia Complementation Group D2 Protein
Female
Genetic Predisposition to Disease
Germ-Line Mutation
Homeodomain Proteins
Humans
LIM Domain Proteins
Middle Aged
Neoplasm Proteins
Pedigree
RNA Helicases
Risk Factors
Transcription Factors
Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer
Tumor Markers, Biological
Oncology & Carcinogenesis
1112 Oncology And Carcinogenesis
Publication Status: Published
Appears in Collections:Division of Surgery
Division of Cancer
Faculty of Medicine



Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Creative Commons