Five recurrent BRCA1/2 mutations are responsible for cancer predisposition in the majority of Slovenian breast cancer families

Krajc, Mateja; Teugels, Erik; Žgajnar, Janez; Goelen, Guido; Bešič, Nikola; Novaković, Srdjan; Hočevar, Marko; Grève, Jacques De

doi:10.1186/1471-2350-9-83

Cited by 36 publications

(39 citation statements)

References 35 publications

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“…The lowest rate of only 10% was present in families with unilateral breast cancer. According to the reported data and also comparing with other studies [25,26,28,29], the presence of ovarian cancer in association with breast cancer serves as a potential predictive factor for BRCA1 mutation positivity and represents the strongest indication. On the other hand, the presence of bilateral ovarian (17%) or breast (13%) cancer is still stronger criterion for selection as the familiar unilateral cancer.…”

Section: Other Hboc Risk Genes -Tp53 Chek2*1100delc Analysismentioning

confidence: 85%

“…Interestingly, a minimum of nonsense mutations was identified in exon 11 [21,25,26,28,29] in comparison to other types of mutations in this exon and no causal missense mutations were present in this exon due to the lack of highly conserved domain in this region. However, it can not be excluded that some of the frequently occurring missense variants with uncertain clinical significance localized mainly in exon 11 (and similarly in exon 16), might have some effect on the protein function and thus play a role in the development of HBOC phenotype.…”

Section: Other Hboc Risk Genes -Tp53 Chek2*1100delc Analysismentioning

confidence: 99%

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Comprehensive genetic characterization of hereditary breast/ovarian cancer families from Slovakia

Konečný

Milly

Zavodna

et al. 2011

Breast Cancer Res Treat

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Germline mutations in the BRCA1/2 genes account for the majority of hereditary breast ovarian cancer (HBOC).Identification of causal mutations may have significant impact on clinical management of such families. Despite high mutation detection rate, many HBOC cases remain without identified cause. These cases warrant use of several analysis methods, such as those for large genomic rearrangements and DNA copy number changes, or analysis other genes, shown to be associated with increased HBOC risk.We assessed 585 Slovak HBOC for presence of mutations in BRCA genes. Sequencing revealed mutations in 100 families, representing 17.1% (88% and 12% of mutations were located in BRCA1 and BRCA2, respectively).Four of the mutations, c.80+4del4, c.1938_1947del10 and c.1166delG in BRCA1 and c.6589delA in BRCA2 gene have been described only in Slovak population. Using MLPA analysis, we detected two large genomic rearrangements in 3 families, a deletion of exons 21 and 22, and a rare deletion of a whole BRCA1 gene. Twentyseven different variants of uncertain clinical effect (4 novel) and 14 distinct SNP BRCA1 haplotypes were detected. Their potential effect was considered using the prediction software packages Align GVGD, Pmut and Polyphen.We observed that the best clinical criterion for the initiation of BRCA1 analysis is the presence of breast cancer at 40 years of age in the association with the presence of ovarian cancer diagnosed around the age of 50.Conversely, the best clinical criterion for starting with BRCA2 analysis is the presence of breast cancer diagnosed in older age (above 50), or the presence of breast cancer in conjunction with carcinomas at different sites e.g. prostate, colorectum, ovary, uterus. Finally we have seen that the analyses of other HBOC risk gene TP53 and specific mutation in CHEK2*c.1100delC in Slovak HBOC families were not efficient since no mutations were found in these genes. 2

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Section: Other Hboc Risk Genes -Tp53 Chek2*1100delc Analysismentioning

confidence: 85%

Section: Other Hboc Risk Genes -Tp53 Chek2*1100delc Analysismentioning

confidence: 99%

Comprehensive genetic characterization of hereditary breast/ovarian cancer families from Slovakia

Konečný

Milly

Zavodna

et al. 2011

Breast Cancer Res Treat

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“…Sokolenko et al found this single mutation to be present in 4% of unilateral breast cancer patients, in 10% of bilateral cancer patients and in 6% of early‐onset cases (diagnosed at or less than age 40) (16). 5382insC is also a founder mutation in Greece (17), Belarus (18), the Czech Republic (19) and Slovenia (20). It is the second most common BRCA1 mutation in the Ashkenazi Jewish population (8, 9).…”

Section: Discussionmentioning

confidence: 99%

The contribution of founder mutations in BRCA1 to breast and ovarian cancer in Lithuania

et al. 2010

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We evaluated the prevalence of BRCA1 founder mutations in unselected cases of breast, ovarian and colon cancer from Lithuania. We identified a founder mutation (4153delA, 5382insC or C61G) in 6% of 235 unselected cases of breast cancer and in 19% of 43 unselected cases of ovarian cancer. Only one patient with a mutation was identified among 178 cases of colon cancer. No mutation was identified among 422 newborn controls. This data indicates that the genetic burden of breast and ovarian cancer attributable to BRCA1 mutations in Lithuania is very high and supports the recommendation that all cases of breast and ovarian cancer in Lithuania be offered genetic testing.

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“…In Poland, this mutation accounts for 2.1% of early‐onset breast cancer cases (<50 years) (11), a much lower prevalence than that observed in Belarus. 5382insC is also a founder mutation in other Slavic countries, such as the Czech Republic (12) Slovenia (13) and northern Greece (14) and is the second most common BRCA1 mutation in the Ashkenazi Jewish population (9, 10).…”

Section: Discussionmentioning

confidence: 99%

The contribution of founder mutations in BRCA1 to breast cancer in Belarus

et al. 2010

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Mutations in the BRCA1 gene increase susceptibility to both breast and ovarian cancer. In some countries, including several in Eastern Europe, founder mutations in the BRCA1 gene are responsible for a significant proportion of breast cancer cases. To estimate the hereditary proportion of breast cancer in Belarus, we sought the presence of any of three founder mutations in BRCA1 (4153delA, 5382insC and C61G) in 500 unselected cases of breast cancer. These mutations have previously been identified in breast/ovarian cancer families from Belarus and from other Slavic countries, including Poland and Russia. One of the three founder mutations in BRCA1 was present in 38 of 500 unselected cases of breast cancer (7.6%). A mutation was found in 12.6% of women diagnosed before age 50 and 5.6% of women diagnosed after age 50. A mutation was identified in 2 of 251 newborn controls (0.8%). The hereditary proportion of breast cancers in Belarus is among the highest of any countries studied to date.

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Five recurrent BRCA1/2 mutations are responsible for cancer predisposition in the majority of Slovenian breast cancer families

Abstract: Background: Both recurrent and population specific mutations have been found in different areas of the world and more specifically in ethnically defined or isolated populations. The population of Slovenia has over several centuries undergone limited mixing with surrounding populations.

Cited by 36 publications

References 35 publications

Comprehensive genetic characterization of hereditary breast/ovarian cancer families from Slovakia

Comprehensive genetic characterization of hereditary breast/ovarian cancer families from Slovakia

The contribution of founder mutations in BRCA1 to breast and ovarian cancer in Lithuania

The contribution of founder mutations in BRCA1 to breast cancer in Belarus

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