ArticleBreast cancer research : BCR2004
The Icelandic founder mutation BRCA2 999del5: analysis of expression.
Article in Breast cancer research : BCR, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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21 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- NSGC practice guideline: risk assessment and genetic counseling for hereditary breast and ovarian cancer.Journal of genetic counseling · 2013Guideline
- Hereditary ovarian cancer.Discover oncology · 2026Review
- A recurrent pathogenic BRCA2 truncating variant reveals a role for BRCA2-PCAF complex in modulating NF-κB-driven transcription.Nature communications · 2025Article
- Review
- Article
- PathogenicCancers · 2021Review
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- Association of Genomic Domains inCancer research · 2020Article
- BRCA1 and BRCA2 pathogenic sequence variants in women of African origin or ancestry.Human mutation · 2019Article
- Association of BRCA2 K3326* With Small Cell Lung Cancer and Squamous Cell Cancer of the Skin.Journal of the National Cancer Institute · 2018Article
- Genetic evaluation and testing for hereditary forms of cancer in the era of next-generation sequencing.Cancer biology & medicine · 2016Article
- Chromosome instability and carcinogenesis: insights from murine models of human pancreatic cancer associated with BRCA2 inactivation.Molecular oncology · 2014Review
- Tumour suppressor mechanisms in the control of chromosome stability: insights from BRCA2.Molecules and cells · 2014Review
- Hereditary breast cancer in the Han Chinese population.Journal of epidemiology · 2013Review
- Common variants of the BRCA1 wild-type allele modify the risk of breast cancer in BRCA1 mutation carriers.Human molecular genetics · 2011Article
- The Leu33Pro polymorphism in the ITGB3 gene does not modify BRCA1/2-associated breast or ovarian cancer risks: results from a multicenter study among 15,542 BRCA1 and BRCA2 mutation carriers.Breast cancer research and treatment · 2010Article
- Common variants in LSP1, 2q35 and 8q24 and breast cancer risk for BRCA1 and BRCA2 mutation carriers.Human molecular genetics · 2009Article
- A role of BRCA1 and BRCA2 germline mutations in breast cancer susceptibility within Sardinian population.BMC cancer · 2009Article
- RAD51 135G-->C modifies breast cancer risk among BRCA2 mutation carriers: results from a combined analysis of 19 studies.American journal of human genetics · 2007Article
- Magnetic techniques for the isolation and purification of proteins and peptides.Biomagnetic research and technology · 2004Article
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4 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
introductionA founder mutation in the BRCA2 gene (BRCA2 999del5) accounts for 7-8% of female breast cancers and for 40% of male breast cancers in Iceland. If expressed, the mutant gene would encode a protein consisting of the first 256 amino acids of the BRCA2 protein. The purpose of this study was to determine whether this mutant protein is produced in heterozygous individuals and, if so, what might be the functional consequences of mutant protein production.
methodsThe presence of BRCA2 999del5 transcripts in fibroblasts from heterozygous individuals was assayed by cDNA synthesis and sequencing. The potential protein-coding portion of BRCA2 999del5 was cloned into the pIND(SP1)/V5-His vector and expressed in COS7 cells. The presence of the mutant protein in cell lysates from heterozygous fibroblasts and from COS7 cells was tested by a number of methods including immunoprecipitation, affinity purification with nickel-coated agarose beads, Western blotting and ELISA, using antibodies to the N-terminal end of BRCA2, antiserum specific for the 16 nonrelevant amino acids at the carboxyl end and antibodies to fusion partners of recombinant proteins.
resultsThe frequency of the BRCA2 999del5 transcript in heterozygous fibroblasts was about one-fifth of the wild-type transcript; however, no mutant protein could be detected. Overexpression of BRCA2 999del5 mRNA in COS7 cells failed to produce a mutant protein unless degradation by proteasomes was blocked.
conclusionOur results show that the protein product of BRCA2 999del5 is extremely unstable. Therefore, an increase in breast cancer risk in BRCA2 999del5 carriers is due to haploinsufficiency at the BRCA2 locus.
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