The deletion of exons 3–5 of BRCA1 is the first founder rearrangement identified in breast and/or ovarian cancer Spanish families

Palanca, Sarai; Juan, Inmaculada de; Pérez-Simó, Gema; Barragán, Eva; Chirivella, Isabel; Martínez, E.; Fuster, Óscar; Bolufer, Pascual

doi:10.1007/s10689-012-9579-6

Cited by 9 publications

(7 citation statements)

References 25 publications

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“…So far, more than 130 LGRs have been identified in the BRCA genes [27]. Most of the LGRs are in BRCA1 , due to the large amount of Alu repeats that comprise it, which makes it susceptible to errors in recombination.…”

Section: Discussionmentioning

confidence: 99%

Mexican BRCA1 founder mutation: Shortening the gap in genetic assessment for hereditary breast and ovarian cancer patients

et al. 2019

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The deletion of exons 9 to 12 of BRCA1 (9–12 del BRCA1) is considered a founder mutation in the Mexican population. We evaluate the usefulness of the target detection of 9–12 del BRCA1 as the first molecular diagnostic strategy in patients with Hereditary Breast and Ovarian Cancer (HBOC). We performed the genetic assessment of 637 patients with suspected HBOC. The region corresponding to the breakpoints for the 9–12 del BRCA1 was amplified by polymerase chain reaction (PCR). An analysis of the clinical data of the carriers and non-carriers was done, searching for characteristics that correlated with the deletion. The 9–12 del BRCA1 was detected in 5% of patients with suspected HBOC (30/637). In patients diagnosed with ovarian cancer, 13 of 30 were 9–12 del BRCA1 carriers, which represents 43%. We found a significant association between the 9–12 del BRCA1 carriers with triple negative breast cancer and high-grade papillary serous ovarian cancer. We concluded that the detection of the 9–12 del BRCA1 is useful as a first molecular diagnostic strategy in the Mexican population. In particular, it shortens the gap in genetic assessment in patients with triple negative breast cancer and ovarian cancer.

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Section: Discussionmentioning

confidence: 99%

Mexican BRCA1 founder mutation: Shortening the gap in genetic assessment for hereditary breast and ovarian cancer patients

et al. 2019

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“…Founder mutations are responsible for the high rates of LGRs in the Valencian Community (Eastern Spain), where NG_005905:g.97346_111983del has deleted BRCA1 exons 3-5 in 10.97% of all families with mutations in the BRCA1 gene [30], and in Portugal, where BRCA2 c.156_157insAluYa5 (NG_012772:g.8686_8687ins AluYa5) accounts for 57.89% of all mutant BRCA2 families [8]. By contrast, in our population deleterious LGRs constitute only 2.34% (95% CI: 0.61–7.22) of all families with definitely pathogenic BRCA1 variants, given the small duplication exon1-2dup cannot be classified as a deleterious mutation.…”

Section: Discussionmentioning

confidence: 99%

Large Genomic Rearrangements of BRCA1 and BRCA2 among Patients Referred for Genetic Analysis in Galicia (NW Spain): Delimitation and Mechanism of Three Novel BRCA1 Rearrangements

et al. 2014

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In the Iberian Peninsula, which includes mainly Spain and Portugal, large genomic rearrangements (LGRs) of BRCA1 and BRCA2 have respectively been found in up to 2.33% and 8.4% of families with hereditary breast and/or ovarian cancer (HBOC) that lack point mutations and small indels. In Galicia (Northwest Spain), the spectrum and frequency of BRCA1/BRCA2 point mutations differs from the rest of the Iberian populations. However, to date there are no Galician frequency reports of BRCA1/BRCA2 LGRs. Here we used multiplex ligation-dependent probe amplification (MLPA) to screen 651 Galician index cases (out of the 830 individuals referred for genetic analysis) without point mutations or small indels. We identified three different BRCA1 LGRs in four families. Two of them have been previously classified as pathogenic LGRs: the complete deletion of BRCA1 (identified in two unrelated families) and the deletion of exons 1 to 13. We also identified the duplication of exons 1 and 2 that is a LGR with unknown pathogenicity. Determination of the breakpoints of the BRCA1 LGRs using CNV/SNP arrays and sequencing identified them as NG_005905.2:g.70536_180359del, NG_005905.2:g.90012_97270dup, and NC_000017.10:g.41230935_41399840delinsAluSx1, respectively; previous observations of BRCA1 exon1-24del, exon1-2dup, and exon1-13del LGRs have not characterized them in such detail. All the BRCA1 LGRs arose from unequal homologous recombination events involving Alu elements. We also detected, by sequencing, one BRCA2 LGR, the Portuguese founder mutation c.156_157insAluYa5. The low frequency of BRCA1 LGRs within BRCA1 mutation carriers in Galicia (2.34%, 95% CI: 0.61–7.22) seems to differ from the Spanish population (9.93%, 95% CI: 6.76–14.27, P-value = 0.013) and from the rest of the Iberian population (9.76%, 95% CI: 6.69–13.94, P-value = 0.014).

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“…The second change, 9254del5 in BRCA2 gene, was also detected in French families [ 65 ]. However, the recent Spanish study introduced exons 3–5 del (g.8097_22733del14637) within the BRCA1 gene as as a new primarily identified Spanish founder mutation among Valencian women [ 66 ]. The most frequent insertion/deletion mutations which occur in this population include c.187_188delAG and c.5385insC in BRCA1 gene and c.9254_9258delATCAT along with c.3492_3493insT in BRCA2 gene.…”

Section: Global Distribution Of Brca1 and mentioning

confidence: 99%

A Comprehensive Focus on Global Spectrum ofBRCA1andBRCA2Mutations in Breast Cancer

Karami

Mehdipour

2013

BioMed Research International

158

115

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Breast cancer (BC) is the most common cancer of women all over the world. BRCA1 and BRCA2 gene mutations comprise the most important genetic susceptibility of BC. Except for few common mutations, the spectrum of BRCA1 and BRCA2 mutations is heterogeneous in diverse populations. 185AGdel and 5382insC are the most important BRCA1 and BRCA2 alterations which have been encountered in most of the populations. After those Ashkenazi founder mutations, 300T>G also demonstrated sparse frequency in African American and European populations. This review affords quick access to the most frequent alterations among various populations which could be helpful in BRCA screening programs.

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The deletion of exons 3–5 of BRCA1 is the first founder rearrangement identified in breast and/or ovarian cancer Spanish families

Cited by 9 publications

References 25 publications

Mexican BRCA1 founder mutation: Shortening the gap in genetic assessment for hereditary breast and ovarian cancer patients

Mexican BRCA1 founder mutation: Shortening the gap in genetic assessment for hereditary breast and ovarian cancer patients

Large Genomic Rearrangements of BRCA1 and BRCA2 among Patients Referred for Genetic Analysis in Galicia (NW Spain): Delimitation and Mechanism of Three Novel BRCA1 Rearrangements

A Comprehensive Focus on Global Spectrum ofBRCA1andBRCA2Mutations in Breast Cancer

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