High proportion of recurrent germline mutations in the BRCA1 gene in breast and ovarian cancer patients from the Prague area

Pohlreich, Petr; Zikán, Michal; Stříbrná, Jana; Kleibl, Zdeněk; Janatová, Markéta; Kotlas, Jaroslav; Zidovská, J; Novotný, Jan; Petruželka, Luboš; Szabo, Csilla I.; Matous, B

doi:10.1186/bcr1282

Cited by 61 publications

(67 citation statements)

References 41 publications

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“…Generally, the most of the pathogenic mutations in this gene in our series are localized in exon 11, similarly to many other reports [31,34,35]. Interestingly, 44% of BRCA2 pathogenic mutations detected in our cohort of patients have also been reported in Czech HBOC population [26,36] confirming the genetic relationship of these two neighbouring populations.…”

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

confidence: 74%

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 Analysissupporting

confidence: 74%

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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“…In the breast cancer patient group BRCA1 founder mutations were detected in 40% and in the ovarian cancer group -in 55% of clinical positive HBOC cases. These data confirm other studies on higher prevalence of BRCA1 gene mutation in families affected with ovarian cancer (Levy-Lahad, 1997;Santarosa et al, 1999;Martin et al, 2001;Pohlreich, 2005). Approximately half of all mutations were detected in patients without cancer inheritance in family.…”

Section: Discussionsupporting

confidence: 91%

“…Overall, the clinical frequency of definitive hereditary breast-ovarian cancer in our study is only 65/1,243 (2.6%), which is approximately three times lower, compared to results of studies from other populations (Pohlreich, 2005;Stacey et al, 2006). In a study by John et al (2004) the clinical frequency of definitive hereditary breast-ovarian cancer in hospital-based breast cancer patients was 204/2,834 (7%).…”

Section: Discussioncontrasting

confidence: 78%

“…In the hereditary breast cancer (HBC) group, from 17 families which had three or more breast cancer cases among first degree relatives we found only one mutation. Compared with other studies, the frequency of the BRCA1 gene mutation in the clinical positive HBC group is much higher (Pohlreich et al, 2005). This underlines the possibility of BRCA1 mutation in other exons, not only three founder mutations (300T/G, 4153delA, 5382 insC) or mutations in the BRCA2 gene.…”

Section: Discussionmentioning

confidence: 46%

See 1 more Smart Citation

Epidemiological, Clinical, Molecular Features and Early Detection Strategy of Most Frequent Hereditary Cancers in Latvia

Gardovskis¹,

Štrumfa²,

Miklaševičs³

et al. 2009

Proceedings of the Latvian Academy of Sciences. Section B. Natural, Exact, and Applied Sciences.

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Contributed by Jânis GardovskisThe aim of the study was to determine epidemiological, clinical and molecular features of hereditary breast-ovarian, colorectal, endometrial, prostate Only 22.0 % of patients were diagnosed with stage I or II disease. The majority of ovarian cancers (78.0 %) were diagnosed with stage III or IV disease. Therefore, it is very important to identify the group at risk from breast and ovarian cancers in order to employ prevention or early detection of cancer in patients and their family members.The majority of breast and ovarian cancers are considered sporadic. Approximately 15-20% of all breast and ovarian cancers are hereditary (Ford et al., 1998;Vasen et al., 2001;Jacobi et al., 2003). The incidence of hereditary breast and ovarian cancer may vary considerably among different populations and ethnic groups. In the last ten years, mutations in both BRCA1 and BRCA2 genes have been shown to be responsible for the development of hereditary breast and ovarian cancer. The aim of the study was to determine clinical and molecular and pathological features of hereditary breast and ovarian cancer in Latvia. There is continuing interest in identifying DNA variants associated with moderately increased risk of cancer. Several studies have suggested an increased risk of cancer in individuals who carry a mutation in the CHEK2 gene, one of the genes in the DNA damage signaling pathway. Originally, a single founder allele in CHEK2, 1100delC, was reported to be a low penetrance breast cancer susceptibility allele in several studies, and in many ethnic groups (Jarvinen, 1992;Bülow et al., 1996; Gorski et al., 2000;Chapelle, 2004). Then, a positive association was found between CHEK2 variants and prostate cancer in the USA, Finland and Poland (Bisgaard et al, 2004;Aretz et al., 2007;Anonîms, 2007). Recently, it was reported that individuals with a single common founder allele in Poland (the I157T missense variant) have increased risk of cancer development in many organs including the breast, prostate, thyroid, kidney and colon (Kilpivaara et al., 2003). The NOD2 gene is associated with susceptibility to inflammatory bowel disease, in particular, with Crohn's disease . It was reported that a single truncating mutation in NOD2, 3020insC, may confer increased risk of late onset colorectal cancer (Ogura et al., 2001) and then that a NOD2 mutation may be associated with increased susceptibility to lung, ovarian, early-onset laryngeal cancer and early onset breast cancer (Lichtenstein et al., 2000). It has not been established whether CHEK2 and NOD2 variants are present in Latvia and whether inherited variation in these genes influences cancer risk in this population.The aim of the study was to investigate the clinical and molecular features of hereditary colorectal cancer syndromes in Latvia in order to offer and provide predictive genetic testing of the affected families.Endometrial cancer. Endometrial cancer (EC) is among the three most common cancers in females in Latvia. There are approximately 390 new c...

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“…The mutational analysis of BRCA1/2 genes in high-risk patients has a mutation pick-up rate of up to 45% (44,54,81).…”

Section: Heritable Gene Defects That Increase the Risk For Common Canmentioning

confidence: 99%

Genetic Bases for Predisposition to Common Multifactorial Disease in Man. Part II

Petkova

Chakarov

Ganev

2007

Biotechnology & Biotechnological Equipment

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High proportion of recurrent germline mutations in the BRCA1 gene in breast and ovarian cancer patients from the Prague area

Abstract: Background Germline mutations in the BRCA1 and BRCA2 genes have been shown to account for the majority of hereditary breast and ovarian cancers. The purpose of our study was to estimate the incidence and spectrum of pathogenic mutations in BRCA1/2 genes in high-risk Czech families.

Cited by 61 publications

References 41 publications

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

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

Epidemiological, Clinical, Molecular Features and Early Detection Strategy of Most Frequent Hereditary Cancers in Latvia

Genetic Bases for Predisposition to Common Multifactorial Disease in Man. Part II

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