<i><scp>BRCA1</scp></i> and <i><scp>BRCA2</scp></i> – update and implications on the genetics of breast cancer: a clinical perspective

Foulkes, William D.

doi:10.1111/cge.12291

Cited by 17 publications

(11 citation statements)

References 51 publications

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“…The PCR products were analysed by agarose gel electrophoresis and Sanger sequencing. The reference sequence NG_005905.2 (NM_007294.3) and traditional numbering of exons [1][2][3][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] was used.…”

Section: Dna and Rna Analysesmentioning

confidence: 99%

The intronic BRCA1 c.5407-25T>A variant causing partly skipping of exon 23—a likely pathogenic variant with reduced penetrance?

et al. 2020

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Rare sequence variants in the non-coding part of the BRCA genes are often reported as variants of uncertain significance (VUS), which leave patients and doctors in a challenging position. The aim of this study was to determine the pathogenicity of the BRCA1 c.5407-25T>A variant found in 20 families from Norway, France and United States with suspected hereditary breast and ovarian cancer. This was done by combining clinical and family information with allele frequency data, and assessment of the variant's effect on mRNA splicing. Mean age at breast (n = 12) and ovarian (n = 11) cancer diagnosis in female carriers was 49.9 and 60.4 years, respectively. The mean Manchester score in the 20 families was 16.4. The allele frequency of BRCA1 c.5407-25T>A was 1/64,566 in non-Finnish Europeans (gnomAD database v2.1.1). We found the variant in 1/400 anonymous Norwegian blood donors and 0/784 in-house exomes. Sequencing of patient-derived cDNA from blood, normal breast and ovarian tissue showed that BRCA1 c.5407-25T>A leads to skipping of exon 23, resulting in frameshift and protein truncation: p.(Gly1803GlnfsTer11). Western blot analysis of transiently expressed BRCA1 proteins in HeLa cells showed a reduced amount of the truncated protein compared with wild type. Noteworthily, we found that a small amount of full-length transcript was also generated from the c.5407-25T>A allele, potentially explaining the intermediate cancer burden in families carrying this variant. In summary, our results show that BRCA1 c.5407-25T>A leads to partial skipping of exon 23, and could represent a likely pathogenic variant with reduced penetrance.

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Section: Dna and Rna Analysesmentioning

confidence: 99%

The intronic BRCA1 c.5407-25T>A variant causing partly skipping of exon 23—a likely pathogenic variant with reduced penetrance?

et al. 2020

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“…Almost 20 years have passed since the genes responsible for increased susceptibility to breastcancerand ovarian familycancer were characterized.This remains the most significant discovery for the genetics of hereditary cancer in humans, in part demonstrated by the fact that almost all ethical-legal debates regarding patents are focused on BRCA1 and BRCA2 genes, with few cases of debate about other genes for cancer susceptibility [3,4]. A woman with a mutation in BRCA1/2 has a risk of up to 87% of developing breast cancer in her lifetime and up to 50% of developing ovarian cancer, but the risk can vary according to the mutation, country of residence, and family history [5,6].…”

Section: Introductionmentioning

confidence: 99%

Founder and Recurrent Mutations in BRCA1 and BRCA2 Genes in Latin American Countries: State of the Art and Literature Review

Ossa

Torres

2016

The Oncologist

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Background. Numerous epidemiological factors affect the probability of developing breast or ovarian cancer, but no predictor is as determinant as inheriting a mutation in BRCA1 or BRCA2. The concept of the founder effect explains the reduced genetic variability in some populations, according to the theory that new populations can be formed from a reduced number of individuals, so the new population would carry only a small fraction of the genetic variability of the original population. The main purpose of this review is to provide an update on the state of the art in founder mutations and some recurrent mutations that have recently been described in Latin America. Methods. A literature search was performed in the electronic databases of PUBMED, EMBASE, LILACS, and BIREME using the terms BRCA1, BRCA2, founder mutation, Latin American population, and Hispanic. Sixty-two papers were identified, of which 38 were considered relevant for this review. Each result is shown per country. Results. In Latin America, clear founder effects have been reported in Mexico (BRCA1 del exons 9-12), Brazil (BRCA1 5382insC and BRCA2 c.156_157insAlu), and Colombia (BRCA1 3450del4, A1708E, and BRCA2 3034del4) and in Latinas residing

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“…About 12 percent of women in the general population will develop breast cancer sometime during their lives [3]. By contrast, according to the most recent estimates, 55 to 65 percent of women who inherit a harmful BRCA1 mutation and around 45 percent of women who inherit a harmful BRCA2 mutation will develop breast cancer by age 70 years [4] Ovarian cancer: About 1.3 percent of women in the general population will develop ovarian cancer sometime during their lives [4]. By contrast, according to the most recent estimates, 39 percent of women who inherit a harmful BRCA1 mutation [5] [6] and 11 to 17 percent of women who inherit a harmful BRCA2 mutation will develop ovarian cancer by age 70 years [5] [6].…”

Section: Risk Factors Of Breast and Ovarian Cancersmentioning

confidence: 99%

Breast and Ovarian Cancer in Young Women of the Arabian Gulf Region: Relationship to Age

Al-Gahtani¹,

Abozaid²,

Al-Nami³

et al. 2016

OJEpi

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It is widely known that cancer is a disease of "old-age". However available data show that this is not the case for many types of cancers. Incidences of breast and ovarian cancers have varying rates of change with age. Breast cancer data of Arabian-gulf women, show that the incidence rates increase with age and reach a maximum at 39 year. It then declines linearly with age to about 55 years. The rate of increase and its changes with age are similar to those of many other countries. In the premenopausal phase the relationship between incidence and age could be adequately modeled using a linear model for the logarithmic transformations of age and incidence. Similar observations are made for the ovarian cancer incidences. Results: It is shown that the rate of increase in breast and ovarian cancer incidence with respect to age is increasing in the premenopausal ages. Moreover, the burden of the disease with respect to mortality and "Disability Adjusted Life Years" or DALY, varied considerably among the six gulf countries. Conclusions: We conclude, based on the age incidence relationship that the number of cancer cases may double in the next period that follows our study period (1998-2009). Moreover, if the six countries have identical relationship between age and the two types of cancer, there should be an integrated and unified effort to have a common strategy for prevention and control.

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BRCA1 and BRCA2 – update and implications on the genetics of breast cancer: a clinical perspective

Cited by 17 publications

References 51 publications

The intronic BRCA1 c.5407-25T>A variant causing partly skipping of exon 23—a likely pathogenic variant with reduced penetrance?

The intronic BRCA1 c.5407-25T>A variant causing partly skipping of exon 23—a likely pathogenic variant with reduced penetrance?

Founder and Recurrent Mutations in BRCA1 and BRCA2 Genes in Latin American Countries: State of the Art and Literature Review

Breast and Ovarian Cancer in Young Women of the Arabian Gulf Region: Relationship to Age

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