Etiology of familial breast cancer with undetected BRCA1 and BRCA2 mutations: clinical implications

Yiannakopoulou, Eugenia

doi:10.1007/s13402-013-0158-0

Cited by 16 publications

(8 citation statements)

References 74 publications

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“…In breast cancer, genes directly affected by hypermethylation include tumor suppressor genes (BRCA1), metastasisinhibitory genes (CDH1, TIMP-3), hormone receptor genes (ER-α, PR) and cell cycle control genes [p16INK4a (CDKN2A)]. 22 , 23 Methylation of the BRCA1 promoter has been shown to occur in approximately 20% of breast cancer patients. Sporadic tumours with BRCA1 promoter methylation have been reported to be ER and PR negative.…”

Section: Resultsmentioning

confidence: 99%

BRCA1 c.68_69delAG (exon2), c.181T>G (exon5), c.798_799delTT and 943ins10 (exon11) mutations in Burkina Faso

Zoure

Slaoui

Bambara

et al. 2018

J Public Health Afr

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The worldwide variation of BRCA mutations is well known. The c.68_69delAG, c.181T>G, c.798_799delTT mutations in BRCA1 were observed in Moroccan, Algerian and Tunisian Breast Cancer families and were described founder mutation in Northern Africa. The 943ins10 is also recognized a founder mutation in West Africa. To our knowledge no study has been published on BRCA1/2 germline mutations and hereditary breast cancer (HBC) in population of Burkina Faso. The aim of the present study (first in Burkina Faso) was to screen for these four mutations in 15 unrelated patients with HBC. Mutation analysis was performed by Sanger sequencing of coding exon2, Exon5 and exon11A sequences of the BRCA1 gene. Blood specimens of 15 patients from Burkina Faso, with HBC were collected at the University Hospital Yalgado OUEDRAOGO (CHU-YO) of Ouagadougou in Burkina Faso. c.68_69delAG (exon2), c.181T>G (exon5), c.798_799delTT and 943ins10 (exon11) mutations were not detected in any of the 15 women diagnosed with family breast cancer history. Genetic analysis in this study, we show that targeting relevant exons in BRCA1 genes did not allow detection of mutations in the population of Burkina Faso. Therefore, such an approach may be of interest to perfom a complete sequencing of BRCA1 and BRCA2 genes in families at a high risk of developing breast cancer in Burkina Faso.

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Section: Resultsmentioning

confidence: 99%

BRCA1 c.68_69delAG (exon2), c.181T>G (exon5), c.798_799delTT and 943ins10 (exon11) mutations in Burkina Faso

Zoure

Slaoui

Bambara

et al. 2018

J Public Health Afr

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“…An estimated 5–10% of all breast cancers are associated with hereditary risk . Familial aggregation of breast cancer in women below age 51 years is mainly due to heritable causes .…”

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confidence: 99%

“…Familial aggregation of breast cancer in women below age 51 years is mainly due to heritable causes . Germline mutations in the BRCA1/2 genes are found in approximately 30% of patients with the family risk . However, the status of HR and other DNA repair pathways in the tumor cells of the remaining vast majority of hereditary breast cancers, particularly hereditary TNBCs, is unknown.…”

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confidence: 99%

BRCA1/2‐negative hereditary triple‐negative breast cancers exhibit BRCAness

Domagała

Hybiak

Cybulski

et al. 2017

Intl Journal of Cancer

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BRCA1/2-associated breast cancers are sensitive to poly(ADPribose) polymerase (PARP) inhibitors and platinum compounds mainly due to their deficiency in DNA repair via homologous recombination (HR). However, approximately only 15% of triple-negative breast cancers (TNBCs) are BRCA1/2-associated. TNBCs that exhibit BRCAness (a phenotype reflecting impaired HR in BRCA1/2-negative tumors) are also regarded sensitive to PARP inhibitors and platinum compounds. Thus, we hypothesized that hereditary BRCA1/2-negative TNBCs may exhibit BRCAness. To find a subset of hereditary BRCA1/2-negative TNBCs among 360 TNBCs, we first identified a group of 41 hereditary TNBCs by analyzing the family histories of the patients. Next, we tested this group for the presence of germline BRCA1/2 mutations, and finally, we compared the expression levels of 120 genes involved in HR and five other major mechanisms of DNA damage repair between BRCA1/2-associated and BRCA1/2-negative subgroups of hereditary TNBCs using real-time PCR arrays. Approximately 73% of the hereditary TNBCs were BRCA1/2-associated and 27% were BRCA1/2-negative. The expression levels of the analyzed genes showed no significant differences between these two subgroups indicating the BRCAness of the BRCA1/2-negative hereditary TNBCs and thereby distinguishing a novel subset of TNBCs as a potential target for PARP inhibitors or platinum-based therapy. The results show the significance of family history in selecting patients with TNBC for therapies directed at incompetent DNA repair (e.g., PARP inhibitors and/or platinum-based therapies) and indicate that a relatively simple strategy for broadening the target group for these modes of treatment is to identify patients with hereditary TNBCs.

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“…It is also reported that most of the families with <6 breast cancer cases and no ovarian cancer do not carry BRCA1 /2 mutations that can be detected by routine sequencing protocols. [7] Various mutations including nonsense mutations, small deletions and insertions, and large genomic rearrangements (LGRs) are reported in BRCA1 gene. [8] Furthermore, these mutations can result in recurrent mutations of other specific genes (such as RB1) that may lead to other cancers.…”

Section: Introductionmentioning

confidence: 99%

Genomic rearrangement screening of the BRCA1 from seventy Iranian high-risk breast cancer families

et al. 2016

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Background:The second leading cause of cancer deaths in women is breast cancer. Germline mutations in susceptibility breast cancer gene BRCA1 increase the lifetime risk of breast cancer. Eighty-one large genomic rearrangements (LGRs) have been reported up to date in BRCA1 gene, and evaluation of these rearrangements helps with precise risk assessment in high-risk individuals. In this study, we have investigated LGRs in BRCA1 among Iranian high-risk breast cancer families.Materials and Methods:Seventy patients with breast cancer who were identified negative for point mutations or small deletions/insertions of BRCA1 gene were selected. Deletions and duplications of BRCA1 gene were evaluated using multiplex ligation-dependent probe amplification (MLPA).Results:Two deletions, deletion of exons 1A/1B-2 and exon 24, were detected in two patients with breast cancer. The former alteration was found in a woman with a strong family history of breast cancer while the latter one was detected in a woman with early onset of breast cancer.Conclusion:Although our data confirm that LGRs in BRCA1 comprise a relatively small proportion of mutations in hereditary breast cancer in the Iranian population, MLPA analysis might be considered for screening of LGRs in high-risk individuals. It is worth to note that our results are consistent with previous studies in various Asian and European countries.

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Etiology of familial breast cancer with undetected BRCA1 and BRCA2 mutations: clinical implications

Cited by 16 publications

References 74 publications

BRCA1 c.68_69delAG (exon2), c.181T>G (exon5), c.798_799delTT and 943ins10 (exon11) mutations in Burkina Faso

BRCA1 c.68_69delAG (exon2), c.181T>G (exon5), c.798_799delTT and 943ins10 (exon11) mutations in Burkina Faso

BRCA1/2‐negative hereditary triple‐negative breast cancers exhibit BRCAness

Genomic rearrangement screening of the BRCA1 from seventy Iranian high-risk breast cancer families

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