Large genomic BRCA2 rearrangements and male breast cancer

Karhu, Ritva; Laurila, Eeva; Kallioniemi, Anne; Syrjäkoski, Kirsi

doi:10.1016/j.cdp.2006.10.002

Cited by 23 publications

(20 citation statements)

References 28 publications

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“…In addition to our previous 4 of 33 MBC cases [4], thus far, only three CHEK2 1100delC cases have been identified worldwide among the additional 627 MBC cases genotyped ( Table 2) [7][8][9][10][11][12][13][14][15][16][17][18]. In contrast to the initial CHEK2 1100delC identification report [4] and our current report, this low frequency of 0.5% (3 of 627 MBC cases) had suggested that CHEK2 1100delC is not a risk allele for MBC.…”

Section: Resultscontrasting

confidence: 72%

“…In contrast to the initial CHEK2 1100delC identification report [4] and our current report, this low frequency of 0.5% (3 of 627 MBC cases) had suggested that CHEK2 1100delC is not a risk allele for MBC. However, most of the reported studies had low CHEK2 1100delC population frequencies and also had used small MBC cohorts [4,[7][8][9][10][11][12][13][14][15][16][17][18], resulting in a lack of statistical power to detect CHEK2 1100delC-associated cancer risks. Interestingly, the Finnish CHEK2 1100delC MBC study had comparable power to our study, but failed to identify a CHEK2 1100delC related MBC risk [13,18].…”

Section: Resultsmentioning

confidence: 99%

“…However, most of the reported studies had low CHEK2 1100delC population frequencies and also had used small MBC cohorts [4,[7][8][9][10][11][12][13][14][15][16][17][18], resulting in a lack of statistical power to detect CHEK2 1100delC-associated cancer risks. Interestingly, the Finnish CHEK2 1100delC MBC study had comparable power to our study, but failed to identify a CHEK2 1100delC related MBC risk [13,18]. Similarly, we previously had identified CHEK2 1100delC as a risk allele for Dutch colorectal cancer cases whereas no such risk could be detected for Finnish colorectal cancer cases [20,25].…”

Section: Resultsmentioning

confidence: 99%

“…In addition to a female breast cancer risk, 4 of 33 (12%) index cases of families with at least one MBC case were CHEK2 1100delC positive suggesting that the mutation also might confer a risk for MBC [4]. Thus far, the prevalence of CHEK2 1100delC in MBC has been evaluated in 12 additional studies [7][8][9][10][11][12][13][14][15][16][17][18]. Yet, only 3 of 627 genotyped samples carried the CHEK2 1100delC mutation, raising doubts on the association of CHEK2 1100delC with MBC.…”

Section: Introductionmentioning

confidence: 99%

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CHEK2 1100delC and male breast cancer in the Netherlands

Wasielewski

Bakker

Ouweland

et al. 2008

Breast Cancer Res Treat

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Mutations in the breast cancer susceptibility genes BRCA1, BRCA2, and CHEK2 are known risk factors for female breast cancer. Mutations in BRCA1 and BRCA2 also are associated with male breast cancer (MBC). Similarly, it had been suggested in the original CHEK2 identification report that the CHEK2 1100delC mutation confers an increased risk for MBC. Here, we have evaluated the risk of CHEK2 1100delC for MBC by genotyping CHEK2 1100delC in 23 familial and 71 unselected Dutch MBC cases. None of the 23 familial MBC cases carried the CHEK2 1100delC mutation. In contrast, CHEK2 1100delC was present in 3 of the 71 (4.2%) unselected MBC cases, which was significantly more prevalent than the 1.1% Dutch population frequency assessed in 1,692 individuals (P = 0.05, OR = 4.1, 95% CI 1.2-14.3). Our data suggest that, in the Netherlands, CHEK2 1100delC is associated with an increased risk for MBC.

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Section: Resultscontrasting

confidence: 72%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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CHEK2 1100delC and male breast cancer in the Netherlands

Wasielewski

Bakker

Ouweland

et al. 2008

Breast Cancer Res Treat

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“…This would make it possible to identify almost every mutation in these high-penetrance genes and to produce a more comprehensive picture of the mutational spectrum in patients with HBOC, which is particularly relevant in families with cases of male breast cancer, where rearrangements in BRCA2 appear to be much more frequent. Approximately 50% of the reported BRCA2 rearrangements have been found in families with cases of male breast cancer [10,18,33,34].…”

Section: Discussionmentioning

confidence: 99%

Identification and comprehensive characterization of large genomic rearrangements in the BRCA1 and BRCA2 genes

Valle

Feliubadaló

Nadal

et al. 2009

Breast Cancer Res Treat

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Large genomic rearrangements are estimated to account for approximately 5-10% of all disease-causing mutations in BRCA1 and BRCA2 genes in patients with hereditary breast and ovarian cancer syndrome (HBOC). We use MRC-Holland Multiplex Ligation-dependent Probe Amplification (MLPA) to screen for such rearrangements in patients with HBOC and as a first step in our genetic testing workflow. The technique was applied to a set of 310 independent patients and detected eight different copy number alterations, corresponding to 2.6% of the studied samples. MLPA was also found to identify point mutations located in probe sequences. As commercial MLPA tests are not suitable for determining the specific breakpoints or for defining the exact extent of rearrangements, we applied a set of different complementary techniques to characterize these genetic alterations with greater precision. Long-range PCR amplification, RNA analysis, SNP-array chips, non-commercial MLPA probes, and FISH analysis were used to fully define the extent and mechanism of each alteration. In BRCA1, six rearrangements were characterized: deletion of E22, duplication of E9-E24, deletion of E16-E23, deletion of E1-E13, deletion of E1-E2 and duplication of E1-E2. In BRCA2, we studied a deletion of E15-E16 and a deletion of E1-E24. To the best of our knowledge, this is the most comprehensive study of the nature and underlying molecular causes of these mutational events in the BRCA1/2 genes.

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