BRCA1 genomic deletions are major founder mutations in Dutch breast cancer patients

Petrij-Bosch, Anne; Peelen, Tamara; Vliet, Martin van; Eijk, Ronald van; Olmer, Renske; Drüsedau, Marion; Hogervorst, Frans B.L.; Hageman, S.; Arts, Peer; Ligtenberg, Marjolijn J. L.; Meijers-Heijboer, Hanne; Klijn, Jan G.M.; Vasen, Hans F. A.; Cornelisse, Cees J.; Veer, Laura J. van’t; Bakker, E; Ommen, G.J.B. van; Devilee, Peter

doi:10.1038/ng1197-341

Cited by 395 publications

(303 citation statements)

References 17 publications

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“…This analysis identifies gene mutations in all of the known protein coding sequences and additional adjacent areas in the genes and detects approximately 90-95% of mutations in BRCA1 and BRCA2. The samples were also analyzed for the presence of five BRCA1 genomic rearrangements using recombination-specific PCR using primers specific for the normal gene as well as for the rearrangement, including: a 3.8-kb deletion of exon 13 and a 510-bp deletion of exon 22 described in individuals of Dutch ancestry [43], a 6-kb duplication of exon 13 described in individuals of European (particularly British) ancestry [44,45], a 7.1-kb deletion of exons 8 and 9 described in individuals of European ancestry [46], and a 26-kb deletion of exons 14-20 [47].…”

Section: Brca1 and Brca2 Analysismentioning

confidence: 99%

Improved survival in BRCA2 carriers with ovarian cancer

et al. 2006

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Objectives-The objective of this study was to investigate survival of ovarian cancer patients with BRCA1 and BRCA2 mutations compared to those without mutations in a population-based sample of incident epithelial ovarian cancer cases. NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript the two analyses were similar, thus data involving the 209 invasive epithelial cancer cases are presented, as this was judged to be more clinically relevant. NIH Public AccessResults-In the multivariate analysis, BRCA status and stage were statistically significant, and were adjusted for in the survival analysis model. The Kaplan-Meier method estimated expected survival at 4 years of 83% of BRCA2 carriers compared to 37% of BRCA1 carriers and 12% of non-carriers. There was a statistically significant difference between BRCA2 carriers and noncarriers (p = 0.013). No statistically significant survival differences were seen for BRCA1 carriers when compared with either BRCA2 carriers or non-carriers.Conclusion-These data suggest that BRCA2 mutation carriers with ovarian cancer may have better survival than BRCA1 carriers and non-carriers. The etiology of this possible survival advantage is currently unknown. Larger studies are needed to confirm these results and to clarify their etiology and clinical significance.

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Section: Brca1 and Brca2 Analysismentioning

confidence: 99%

Improved survival in BRCA2 carriers with ovarian cancer

et al. 2006

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“…PCRproducts were size-fractionated on an ABI377™ DNA sequencer, and those showing additional bands were re-amplified and sequenced. In addition, two PCR-amplifiers specifically detected the junction of the two major large genomic deletions when present (Petrij-Bosch et al, 1997). Based on the currently known mutation incidence among Dutch breast cancer families (http://www.medfac.…”

Section: Populationmentioning

confidence: 99%

Clinical and pathological features of BRCA1 associated carcinomas in a hospital-based sample of Dutch breast cancer patients

Bock¹,

Tollenaar²,

Papelard³

et al. 2001

Br J Cancer

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Several studies have investigated the differences in tumour characteristics between breast cancer in BRCA1-carriers and other patients, aiming to obtain insight into features that might be of importance for recognizing patients with BRCA1-related tumours. In many studies, it was observed that BRCA1-associated breast cancers are more frequently histologic grade 3 (Eisinger et al, 1996;Marcus et al, 1996;Johannsson et al, 1997;Karp et al, 1997;Lakhani et al, 1997;Armes et al, 1998;Lynch et al, 1998) and that they express receptors for oestrogen and progesterone less frequently (Johannsson et al, 1997;Karp et al, 1997;Lynch et al, 1998;Loman et al, 1998Verhoog et al, 1998Armes et al, 1999). Both features are usually associated with a poorer prognosis.However, all studies were performed on highly selected groups of patients, which might lead to survival bias and underestimation of the differences under study. The majority of studies examined tumours from families with a high incidence of breast cancer (Eisinger et al, 1996;Marcus et al, 1996;Johannsson et al, 1997;Lakhani et al, 1997;Loman et al, 1998;Lynch et al, 1998;Verhoog et al, 1998), from patients with an early onset breast cancer (Armes et al, 1998(Armes et al, , 1999, or from specific populations with founder mutations (Karp et al, 1997). Moreover, in most studies in which the cases were selected from breast cancer families, the controls were breast cancer patients without a positive family history but no definite proof of a negative BRCA1 mutations status (Eisinger et al, 1996;Verhoog et al, 1998) or an unknown family history (Marcus et al, 1996;Johannsson et al, 1997;Lakhani et al, 1997). This might also give an underestimation of the differences under study.Recently, we completed a BRCA1 mutation screening study on a hospital-based cohort of 642 breast cancer patients not selected for family history or age at diagnosis. BRCA1-germline mutations were identified in 10 patients by using a mutation-scanning assay that would detect approximately 70% of the currently known Dutch mutation spectrum (Papelard et al, 2000). The aim of this analysis is to investigate the clinical and pathological features of these BRCA1 associated carcinomas as compared to other breast cancers in a representative sample. METHODS Patients and SettingPopulation From January 1984 until November 1996 all primary invasive breast cancer patients surgically treated at the Leiden University Medical Centre (LUMC) regardless of age or family history have been asked to provide a blood sample for research purposes. Mutation screening of BRCA1 was performed anonymously using an assay targeted at known founder mutations in the Dutch population. In brief, 15 PCR-amplifiers covered gene regions known to Summary Thus far, studies investigating the differences in tumour characteristics between breast cancer in BRCA1-carriers and other patients, have focused on highly selected groups of patients, potentially limiting the conclusions that can be drawn. Previously, we had identified 10 patients with BR...

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“…For example, it can help us better understand the genetic causes of certain diseases and as a consequence, improve the treatment and prognosis of individual patients. Classic techniques for the detection of chromosomal abnormalities include karyotyping, Southern blotting, Fluorescent In Situ Hybridisation (FISH), CA-repeat analysis and quantitative micro satellite analysis by real-time PCR [1-4]. In recent years, high-throughput methods based on BAC arrays, SNP arrays and related techniques have gained prominence [5,6].…”

Section: Introductionmentioning

confidence: 99%

MLPAinter for MLPA interpretation: an integrated approach for the analysis, visualisation and data management of Multiplex Ligation-dependent Probe Amplification

et al. 2010

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BackgroundMultiplex Ligation-Dependent Probe Amplification (MLPA) is an application that can be used for the detection of multiple chromosomal aberrations in a single experiment. In one reaction, up to 50 different genomic sequences can be analysed. For a reliable work-flow, tools are needed for administrative support, data management, normalisation, visualisation, reporting and interpretation.ResultsHere, we developed a data management system, MLPAInter for MLPA interpretation, that is windows executable and has a stand-alone database for monitoring and interpreting the MLPA data stream that is generated from the experimental setup to analysis, quality control and visualisation. A statistical approach is applied for the normalisation and analysis of large series of MLPA traces, making use of multiple control samples and internal controls.ConclusionsMLPAinter visualises MLPA data in plots with information about sample replicates, normalisation settings, and sample characteristics. This integrated approach helps in the automated handling of large series of MLPA data and guarantees a quick and streamlined dataflow from the beginning of an experiment to an authorised report.

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BRCA1 genomic deletions are major founder mutations in Dutch breast cancer patients

Cited by 395 publications

References 17 publications

Improved survival in BRCA2 carriers with ovarian cancer

Improved survival in BRCA2 carriers with ovarian cancer

Clinical and pathological features of BRCA1 associated carcinomas in a hospital-based sample of Dutch breast cancer patients

MLPAinter for MLPA interpretation: an integrated approach for the analysis, visualisation and data management of Multiplex Ligation-dependent Probe Amplification

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