Background: The Sardinian population is genetically homogeneous and could be useful in understanding better the genetics of a complex disease like breast cancer (BC). Patients and methods: Using a screening assay based on a combination of single-strand conformation polymorphism, denaturing high-performance liquid chromatography and sequence analysis, 47 Sardinian families with three or more BC cases were screened for germline mutations in BRCA1 and BRCA2 genes. Results: Three BRCA1/2 germline sequence variants were identified. While BRCA2-Ile3412Val is a missense variant with unknown functional significance, BRCA2-8765delAG and BRCA1-Lys505ter are two deleterious mutations (due to their predicted effects on protein truncation), which were found in seven families (15%). BRCA2-8765delAG was found in six of eight (75%) BRCA1/2-positive families and seven of 501 (1.4%) unselected and consecutively collected BC patients. Prevalence of BRCA1/2 mutations in BC families was significantly correlated with the total number of female BCs (P < 0.01) and increased by the presence of (i) at least one case of ovarian or male BC, or (ii) three generations affected, or (iii) bilateral BC. Conclusions: Identification of such features should address BC patients and their families to genetic counseling and BRCA1/2 mutational analysis. In addition, this is the first report of a detailed BRCA1/2 mutation screening in Sardinia, having immediate implications for the clinical management of BC families.
Background: The Sardinian population is genetically homogeneous and could be useful in understanding better the genetics of a complex disease like breast cancer (BC). Patients and methods: Using a screening assay based on a combination of single-strand conformation polymorphism, denaturing high-performance liquid chromatography and sequence analysis, 47 Sardinian families with three or more BC cases were screened for germline mutations in BRCA1 and BRCA2 genes. Results: Three BRCA1/2 germline sequence variants were identified. While BRCA2-Ile3412Val is a missense variant with unknown functional significance, BRCA2-8765delAG and BRCA1-Lys505ter are two deleterious mutations (due to their predicted effects on protein truncation), which were found in seven families (15%). BRCA2-8765delAG was found in six of eight (75%) BRCA1/2-positive families and seven of 501 (1.4%) unselected and consecutively collected BC patients. Prevalence of BRCA1/2 mutations in BC families was significantly correlated with the total number of female BCs (P < 0.01) and increased by the presence of (i) at least one case of ovarian or male BC, or (ii) three generations affected, or (iii) bilateral BC. Conclusions: Identification of such features should address BC patients and their families to genetic counseling and BRCA1/2 mutational analysis. In addition, this is the first report of a detailed BRCA1/2 mutation screening in Sardinia, having immediate implications for the clinical management of BC families.
BRCA1 and BRCA2 germline mutations in Sardinian breast cancer families and their implications for genetic counseling / Palmieri, G; Palomba, G; Cossu, A; Pisano, M; Dedola, Mf; Sarobba, Mg; Farris, A; Olmeo, N; Contu, A; Pasca, A; Satta, Mp; Persico, I; Carboni, Aa; COSSU ROCCA, Paolo Alessandro; Contini, M; Mangion, J; Stratton, Mr; Tanda, Francesco. - In: ANNALS OF ONCOLOGY. - ISSN 0923-7534. - 13:12(2002), pp. 1899-1907. [10.1093/annonc/mdf326]
BRCA1 and BRCA2 germline mutations in Sardinian breast cancer families and their implications for genetic counseling
Palmieri G;Cossu A;COSSU ROCCA, Paolo Alessandro;TANDA, Francesco
2002-01-01
Abstract
Background: The Sardinian population is genetically homogeneous and could be useful in understanding better the genetics of a complex disease like breast cancer (BC). Patients and methods: Using a screening assay based on a combination of single-strand conformation polymorphism, denaturing high-performance liquid chromatography and sequence analysis, 47 Sardinian families with three or more BC cases were screened for germline mutations in BRCA1 and BRCA2 genes. Results: Three BRCA1/2 germline sequence variants were identified. While BRCA2-Ile3412Val is a missense variant with unknown functional significance, BRCA2-8765delAG and BRCA1-Lys505ter are two deleterious mutations (due to their predicted effects on protein truncation), which were found in seven families (15%). BRCA2-8765delAG was found in six of eight (75%) BRCA1/2-positive families and seven of 501 (1.4%) unselected and consecutively collected BC patients. Prevalence of BRCA1/2 mutations in BC families was significantly correlated with the total number of female BCs (P < 0.01) and increased by the presence of (i) at least one case of ovarian or male BC, or (ii) three generations affected, or (iii) bilateral BC. Conclusions: Identification of such features should address BC patients and their families to genetic counseling and BRCA1/2 mutational analysis. In addition, this is the first report of a detailed BRCA1/2 mutation screening in Sardinia, having immediate implications for the clinical management of BC families.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.