Identification of a founder BRCA2 mutation in Sardinian breast cancer families

Monne, Maria; Piras, Giovanna; Fancello, Patrizia; Santona, Maria Cristina; Uras, Antonella; Landriscina, Gennaro; Mastio, Giuseppe; Gabbas, Attilio

doi:10.1007/s10689-006-9107-7

Cited by 7 publications

(8 citation statements)

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“…In particular, cases carrying the BRCA2 c.8764_8765delAG mutation belonged to unrelated families originating from different villages in the northern part of the island [11,14]; most of families genotyped with markers flanking the BRCA2 gene at 13q12-q13 locus were demonstrated to share a large haplotype, not found in control chromosomes from the same geographical area [11]. Conversely, the BRCA2 c.3950_3952delTAGinsAT , which was previously reported as a founder mutation, was instead running in families belonging to a single extended pedigree confined to a small village of the central part of Sardinia [19]. The BRCA1 variants occurred in families originating from different areas of the island without a defined geographical clustering, though about half of the cases carrying the BRCA1 mutations originated from the South Sardinia.…”

Section: Discussionmentioning

confidence: 99%

“…Three-hundred-forty-eight (32%) presented a familial recurrence of invasive breast or ovarian carcinoma: 237 originated from North Sardinia, 66 from Middle and 45 from South. Part of the present cohort (112 familial cases with at least three affected members) had been already included in our previous studies [18,19]. The remaining 737 (68%) breast cancer patients were sporadic cases.…”

Section: Methodsmentioning

confidence: 99%

“…Genomic DNA was obtained from isolated white blood cells by salting out procedure [20]. Mutation detection for all coding regions and splice boundaries of BRCA1 and BRCA2 genes was performed by single strand conformation polymorphism (SSCP) for a small fraction of cases (27 family probands); all remaining cases underwent mutational screening by denaturing high performance liquid chromatography (DHPLC), using the WAVE Nucleic Acid Fragment Analysis System (Transgenomic, Omaha, NE), followed by automated sequencing as previously reported [18,19]. To confirm that each germline variant detected by sequencing was a real mutation and not a polymorphism, 103 unrelated normal individuals (corresponding to 206 chromosomes), originating from the same geographical area and with no family history for breast cancer, were used as controls and screened for each gene variant identified.…”

Section: Methodsmentioning

confidence: 99%

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A role of BRCA1 and BRCA2germline mutations in breast cancer susceptibility within Sardinian population

Palomba

Loi

Uras³

et al. 2009

BMC Cancer

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BackgroundIn recent years, numerous studies have assessed the prevalence of germline mutations in BRCA1 and BRCA2 genes in various cohorts. We here extensively investigated the prevalence and geographical distribution of BRCA1-2 mutations in the entire genetically-homogeneous Sardinian population. The occurrence of phenotypic characteristics which may be predictive for the presence of BRCA1-2 germline mutations was also evaluated.MethodsThree hundred and forty-eight breast cancer patients presenting a familial recurrence of invasive breast or ovarian carcinoma with at least two affected family members were screened for BRCA1-2 mutations by DHPLC analysis and DNA sequencing. Association of BRCA1 and BRCA2 mutational status with clinical and pathological parameters was evaluated by Pearson's Chi-Squared test.Results and ConclusionOverall, 8 BRCA1 and 5 BRCA2 deleterious mutations were detected in 35/348 (10%) families; majority (23/35;66%) of mutations was found in BRCA2 gene. The geographical distribution of BRCA1-2 mutations was related to three specific large areas of Sardinia, reflecting its ancient history: a) the Northern area, linguistically different from the rest of the island (where a BRCA2 c.8764_8765delAG mutation with founder effect was predominant); b) the Middle area, land of the ancient Sardinian population (where BRCA2 mutations are still more common than BRCA1 mutations); and c) the South-Western area, with many Phoenician and Carthaginian locations (where BRCA1 mutations are prevalent). We also found that phenotypic features such as high tumor grading and lack of expression of estrogen/progesterone receptors together with age at diagnosis and presence of ovarian cancer in the family may be predictive for the presence of BRCA1-2 germline mutations.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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A role of BRCA1 and BRCA2germline mutations in breast cancer susceptibility within Sardinian population

Palomba

Loi

Uras³

et al. 2009

BMC Cancer

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“…Nonetheless, a few founder recurrent mutations in BRCA1 [2][3][4] and BRCA2 [5,6] originated from different regions of Italy have been observed.…”

Section: Introductionmentioning

confidence: 99%

Founder mutations account for the majority of BRCA1-attributable hereditary breast/ovarian cancer cases in a population from Tuscany, Central Italy

Papi

Putignano

Congregati

et al. 2008

Breast Cancer Res Treat

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The observation that a high proportion of families with BRCA1 alterations from Central-Eastern Tuscany harbours a limited number of founder mutations can have significant impact on clinical management of at risk subjects from this area. In addition, the identification of a large set of families carrying an identical mutation that predisposes to breast and ovarian cancer provides unique opportunities to study the effect of other genetic and environmental factors on penetrance and disease phenotype.

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“…Another study of 2007 described the BRCA2 3952del TAGinsAT mutations in six patients from a small village of the central part of Sardinia and with a family history of breast cancer. The haplotype analyses suggests that all mutation carriers had a common ancestor, proving the founder effect in Middle Sardinia population [64].…”

Section: Founder Mutations In Sardiniamentioning

confidence: 70%

Identification and Characterization of BRCA1 and BRCA2 Founder Mutations

Sidoni

Cocciolone

Giannini³

et al. 2012

CWHR

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A large number of cancer predisposing BRCA1/BRCA2 mutations have been reported, with a wide variety among populations. In some restricted groups, specific germline mutations in these tumor suppressor genes have been found with high predominance, due to a founder effect. We focused our review on the Italian founder mutations. The first Italian BRCA1 founder mutation, 5083del19, was found in Calabria: the presence of common allele in all carriers of this mutation (also in families with Calabrian origin living in other parts of Italy) confirmed its founder effect. The same BRCA1 mutation was identified in the Sicilian population, but only the haplotype analysis can reveal the common ancestor of these groups. Another BRCA1 founder mutation, 4843delC, was found in Sicily. Four distinct BRCA1 mutations are attributable to families original from Tuscany: 3348delAG, 3285delA, 1499insA and 5183delTGT; the latter has been shown to be a founder mutation from North-Eastern Italy. The first BRCA2 mutation was identified in Sardinia, 8765delAG, a mutation already described as a founder mutation in Jewish-Yemenite families and also in French-Canadian population but with independent origins of carriers in these three populations. BRCA2 3951del3 and BRCA1 917delTT have been described as founder mutations in Middle Sardinia and in South and Middle Sardinia, respectively. Studies regarding prevalence and penetrance of founder mutations can allow to quantify the degree of homogeneity within a population and can surely help the geneticist and oncologist to simplify their choices in the genetic testing on high-risk families, on the basis of their ethnical origin

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Identification of a founder BRCA2 mutation in Sardinian breast cancer families

Cited by 7 publications

References 20 publications

A role of BRCA1 and BRCA2germline mutations in breast cancer susceptibility within Sardinian population

A role of BRCA1 and BRCA2germline mutations in breast cancer susceptibility within Sardinian population

Founder mutations account for the majority of BRCA1-attributable hereditary breast/ovarian cancer cases in a population from Tuscany, Central Italy

Identification and Characterization of BRCA1 and BRCA2 Founder Mutations

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