Novel germline mutations in BRCA2 gene among breast and breast-ovarian cancer families from Poland

Bałabas, Aneta; Skasko, E.; Nowakowska, Dorota; Niwińska, Anna; Blecharz, Paweł

doi:10.1007/s10689-010-9338-5

Cited by 5 publications

(3 citation statements)

References 21 publications

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“…Two patients carried the likely pathogenic BRCA2 mutation c.9371A > T. This substitution is located in an evolutionarily conserved region of the BRCA2 gene and is predicted to adversely affect ssDNA interaction and the structural integrity of the C-terminal domain of the protein [ 40 , 41 ]. This variant has previously been reported in 11 unrelated patients from Poland (Table 3 ) [ 25 , 34 , 36 , 42 ]. Kluska et al recently identified the variant in six patients and proposed its inclusion in the list of Polish founder mutations [ 25 ].…”

Section: Discussionmentioning

confidence: 66%

Recurrent mutations of BRCA1, BRCA2 and PALB2 in the population of breast and ovarian cancer patients in Southern Poland

Wójcik¹,

Jasiówka

Strycharz³

et al. 2016

Hered Cancer Clin Pract

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BackgroundMutations in the BRCA1, BRCA2 and PALB2 genes are well-established risk factors for the development of breast and/or ovarian cancer. The frequency and spectrum of mutations in these genes has not yet been examined in the population of Southern Poland.MethodsWe examined the entire coding sequences of the BRCA1 and BRCA2 genes and genotyped a recurrent mutation of the PALB2 gene (c.509_510delGA) in 121 women with familial and/or early-onset breast or ovarian cancer from Southern Poland.ResultsA BRCA1 mutation was identified in 11 of 121 patients (9.1 %) and a BRCA2 mutation was identified in 10 of 121 patients (8.3 %). Two founder mutations of BRCA1 accounted for 91 % of all BRCA1 mutation carriers (c.5266dupC was identified in six patients and c.181 T > G was identified in four patients). Three of the seven different BRCA2 mutations were detected in two patients each (c.9371A > T, c.9403delC and c.1310_1313delAAGA). Three mutations have not been previously reported in the Polish population (BRCA1 c.3531delT, BRCA2 c.1310_1313delAAGA and BRCA2 c.9027delT). The recurrent PALB2 mutation c.509_510delGA was identified in two patients (1.7 %).ConclusionsThe standard panel of BRCA1 founder mutations is sufficiently sensitive for the identification of BRCA1 mutation carriers in Southern Poland. The BRCA2 mutations c.9371A > T and c.9403delC as well as the PALB2 mutation c.509_510delGA should be included in the testing panel for this population.

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Section: Discussionmentioning

confidence: 66%

Recurrent mutations of BRCA1, BRCA2 and PALB2 in the population of breast and ovarian cancer patients in Southern Poland

Wójcik¹,

Jasiówka

Strycharz³

et al. 2016

Hered Cancer Clin Pract

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“…The incidence of SNVs and indels within 167 amplicons covering the BRCA1 and BRCA2 exons was tested using the Ion Torrent PGM sequencer in 31 (a training set) and 512 women with breast cancer or ovarian cancer newly diagnosed before the age of 50 years who were positive and negative for BRCA1/2 mutations, respectively, as determined by targeted genotyping. The genotyping comprised 11 mutations in BRCA1 , namely c.66_67delAG, C61R, c.3700_3704del5, c.3756delGTCT, c.3777delT, c.4035delA, c.4041delAG, c.4065delTCAA, c.5263delC, R1738E and R1751X, and nine mutations in BRCA2 , namely E394X, c.5239insT, c.5946delT, c.5964delAT, c.6447delTA, c.7910del5, c.8924delT, R3128X and c.9402delT [ 7 , 30 ]. Of the 512 women, 317 had familial breast and/or ovarian cancer, and 195 had only early onset cancer and/or contralateral breast and ovarian cancers; the median age of women with breast cancer at diagnosis was 43 years.…”

Section: Resultsmentioning

confidence: 99%

“… *Eleven BRCA1 mutations (c.66_67delAG, C61R, c.3700_3704del5, c.3756delGTCT, c.3777delT, c.4035delA, c.4041delAG, c.4065delTCAA, c.5263delC, R1738E and R1751X) and nine BRCA2 mutations (E394X, c.5239insT, c.5946delT, c.5964delAT, c.6447delTA, c.7910del5, c.8924delT, R3128X and c.9402delT) [ 7 , 30 ]. #family tree is depicted in Additional file 2 .…”

Section: Discussionmentioning

confidence: 99%

New recurrent BRCA1/2 mutations in Polish patients with familial breast/ovarian cancer detected by next generation sequencing

et al. 2015

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BackgroundTargeted PCR-based genetic testing for BRCA1 and BRCA2 can be performed at a lower cost than full gene testing; however, it may overlook mutations responsible for familial breast and/or ovarian cancers. In the present study, we report the utility of next generation sequencing (NGS) to identify new pathogenic variants of BRCA1/2.MethodsBRCA1 and BRCA2 exons were amplified using the Ion AmpliSeq BRCA1/2 Panel and sequenced on the Ion Torrent PGM sequencer in 512 women with familial and/or only early onset breast and/or ovarian cancers who were negative for selected BRCA1/2 mutations.Results146 single nucleotide variants (SNVs) and 32 indels were identified. Of them, 14 SNVs and 17 indels were considered as pathogenic or likely pathogenic. One and 18 pathogenic mutations had been detected previously in the Polish and other populations, respectively, and 12 deleterious mutations were previously unknown. Eight mutations were recurrent; Q563X (BRCA1), N3124I (BRCA2) and c.4516delG (BRCA1) were found in eight, six and four patients, respectively, and two other mutations (c.9118-2A > G and c.7249delCA in BRCA2) were detected in three patients each. Altogether, BRCA1/2 pathogenic mutations were identified in 52 out of 512 (10%) patients.ConclusionsNGS substantially improved the detection rates of a wide spectrum of mutations in Polish patients with familial breast and/or ovarian cancer. Although targeted screening for specific BRCA1 mutations can be offered to all Polish breast or ovarian cancer patients, NGS-based testing is justified in patients with breast or ovarian cancer likely related to BRCA1/2 who test negative for the selected BRCA1/2 pathogenic mutations.Electronic supplementary materialThe online version of this article (doi:10.1186/s12920-015-0092-2) contains supplementary material, which is available to authorized users.

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High frequency of BRCA1 founder mutations in Polish women with nonfamilial breast cancer

et al. 2012

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Possession of a BRCA1/2 mutation increases risk of contralateral breast and ovarian cancer recurrence and may have an impact on health management decisions, such as imaging screening, preventive surgical interventions and systemic therapies. A hospital-based study was conducted to assess the frequency and spectrum of pathogenic germline BRCA1 and BRCA2 mutations in Polish women with familial and nonfamilial breast cancer. Genomic DNA was extracted from 1581 women with breast cancer and from 2225 healthy individuals. For genotyping BRCA1 (5382insC, T300G, 3819del5, 185delAG, C5370T, 3875del4, 3896delT, 4153delA, 4184del4, 4160delAG, G5332A) mutations and BRCA2 (G1408T, 5467insT, 6174delT, 6192delAT, 6675delTA, 8138del5, 9152delT, C9610T, 9630delC) mutations, a Custom TaqMan (Applied Biosystems) PCR-based technology was adopted. A BRCA1 mutation was found in 26 and 12.5 % of women with familial breast cancer and in 13 and 8.3 % nonfamilial (sporadic) breast cancer, diagnosed before or after 50 years of age, respectively. A much lower frequency of BRCA2 mutation was observed. The predominance of seven BRCA1 mutations (5382insC, T300G, 3819del5, 185delAG, C5370T, 3875del4, 4153delA) studied in the Masovian voivodeship population confirmed a strong founder effect for BRCA1 mutations in the Polish population, and the results of BRCA2 testing confirmed a high diversity in the studied pathogenic mutations in BRCA2 gene. We propose offering inexpensive testing for the presence of BRCA1 founder mutations to all Polish women at the time of initial breast cancer diagnosis, regardless of the patient's family history or age of disease onset.

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Novel germline mutations in BRCA2 gene among breast and breast-ovarian cancer families from Poland

Cited by 5 publications

References 21 publications

Recurrent mutations of BRCA1, BRCA2 and PALB2 in the population of breast and ovarian cancer patients in Southern Poland

Recurrent mutations of BRCA1, BRCA2 and PALB2 in the population of breast and ovarian cancer patients in Southern Poland

New recurrent BRCA1/2 mutations in Polish patients with familial breast/ovarian cancer detected by next generation sequencing

High frequency of BRCA1 founder mutations in Polish women with nonfamilial breast cancer

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