BRCA1 and BRCA2 germline mutations in Sardinian breast cancer families and their implications for genetic counseling

Palmieri, Giuseppe; Palomba, Grazia; Cossu, Antonio; Pisano, Marina; Dedola, Maria Filomena; Sarobba, Maria Giuseppa; Farris, A.; Olmeo, N.; Contu, A.; Pasca, A; Satta, Maria Paola; Persico, Ivana; Carboni, A.; Cossu-Rocca, Paolo; Contini, M; Mangion, Jonathan; Stratton, Michael R.; Tanda, Francesco

doi:10.1093/annonc/mdf326

Cited by 21 publications

(17 citation statements)

References 23 publications

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“…Although it has been estimated that the percentage of hereditary breast carcinoma in Sardinia is comparable to that observed in other genetically homogeneous populations, 25,27 the prevalence of our BRCA2 founder mutation was lower than expected. Three BRCA1 founder mutations account for the vast majority of breast carcinoma families among Ashkenazi Jews, 22 and a single BRCA2 mutation accounts for nearly all breast-ovarian carcinoma families in Iceland.…”

Section: Discussioncontrasting

confidence: 51%

Spectrum and prevalence of BRCA1 and BRCA2 germline mutations in Sardinian patients with breast carcinoma through hospital‐based screening

Palomba

Pisano

Cossu

et al. 2005

Cancer

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Section: Discussioncontrasting

confidence: 51%

Spectrum and prevalence of BRCA1 and BRCA2 germline mutations in Sardinian patients with breast carcinoma through hospital‐based screening

Palomba

Pisano

Cossu

et al. 2005

Cancer

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“…In the present study, we found BRCA1/2 mutations in the 29.4% of BC/OC families from Barbagia, a proportion similar to that estimated in high-risk BC families from the northern part of Sardinia [14]. Four of five BRCA1/BRCA2 changes detected in this study were novel mutations not reported in the BIC database, pointing to the genetic peculiarity of the Barbagia population.…”

Section: Discussionsupporting

confidence: 85%

“…In Italy, a regional founder effect has been demonstrated for the mutation BRCA1 5083del19 and for the BRCA2 8765delAG which has been identified in the northern part of Sardinia [12][13][14].…”

Section: Introductionmentioning

confidence: 98%

Identification of a founder BRCA2 mutation in Sardinian breast cancer families

Monne¹,

Piras²,

Fancello³

et al. 2007

Familial Cancer

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The population of Sardinia is characterized by a relatively low level of genetic heterogeneity: therefore 'founder mutations' can be expected to be found. We analysed 17 probands from families with high incidence of breast cancer or breast and ovarian cancer by sequencing the full-length coding regions of BRCA1 and BRCA2 genes. A novel BRCA2 frame-shift mutation, 3951del3insAT, which produces a protein truncated at codon 1258, was observed in six patients with BC from the same village. The mutation was not found in unaffected females (matched on basis of ethnicity and age) with no family history of cancer. Haplotype analysis strongly suggests that all affected persons had a common ancestor. The identification of this clinically significant founder mutation may facilitate screening/testing for inherited risk of breast cancer.

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“…In Sardinia, whose population is genetically homogeneous due to the fact that it is relatively isolated and with high rate of inbreeding, the contribution of BRCA mutations to the population incidence of breast cancer has been evaluated by our group in recent past years [23-25]. Three deleterious BRCA germline mutations have been observed in about 15% families and in about 3% non-familial breast cancer patients from North Sardinia ( BRCA2 mutations were the most prevalent BRCA sequence variations and a single variant, BRCA2-8765delAG , was the most recurrent mutation with a founder effect in our population) [23-25].…”

Section: Introductionmentioning

confidence: 99%

Role of BRCA2 mutation status on overall survival among breast cancer patients from Sardinia

Budroni

Cesaraccio

Coviello³

et al. 2009

BMC Cancer

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BackgroundGermline mutations in BRCA1 or BRCA2 genes have been demonstrated to increase the risk of developing breast cancer. Conversely, the impact of BRCA mutations on prognosis and survival of breast cancer patients is still debated. In this study, we investigated the role of such mutations on breast cancer-specific survival among patients from North Sardinia.MethodsAmong incident cases during the period 1997–2002, a total of 512 breast cancer patients gave their consent to undergo BRCA mutation screening by DHPLC analysis and automated DNA sequencing. The Hakulinen, Kaplan-Meier, and Cox regression methods were used for both relative survival assessment and statistical analysis.ResultsIn our series, patients carrying a germline mutation in coding regions and splice boundaries of BRCA1 and BRCA2 genes were 48/512 (9%). Effect on overall survival was evaluated taking into consideration BRCA2 carriers, who represented the vast majority (44/48; 92%) of mutation-positive patients. A lower breast cancer-specific overall survival rate was observed in BRCA2 mutation carriers after the first two years from diagnosis. However, survival rates were similar in both groups after five years from diagnosis. No significant difference was found for age of onset, disease stage, and primary tumour histopathology between the two subsets.ConclusionIn Sardinian breast cancer population, BRCA2 was the most affected gene and the effects of BRCA2 germline mutations on patients' survival were demonstrated to vary within the first two years from diagnosis. After a longer follow-up observation, breast cancer-specific rates of death were instead similar for BRCA2 mutation carriers and non-carriers.

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BRCA1 and BRCA2 germline mutations in Sardinian breast cancer families and their implications for genetic counseling

Cited by 21 publications

References 23 publications

Spectrum and prevalence of BRCA1 and BRCA2 germline mutations in Sardinian patients with breast carcinoma through hospital‐based screening

Spectrum and prevalence of BRCA1 and BRCA2 germline mutations in Sardinian patients with breast carcinoma through hospital‐based screening

Identification of a founder BRCA2 mutation in Sardinian breast cancer families

Role of BRCA2 mutation status on overall survival among breast cancer patients from Sardinia

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