BRCA1 and BRCA2 germline mutations in Sardinian breast cancer families and their implications for genetic counseling
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-perf...
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| Veröffentlicht in: | Annals of oncology 2002-12, Vol.13 (12), p.1899-1907 |
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| creator | Palmieri, G. Palomba, G. Cossu, A. Pisano, M. Dedola, M. F. Sarobba, M. G. Farris, A. Olmeo, N. Contu, A. Pasca, A. Satta, M. P. Persico, I. Carboni, A. A. Cossu-Rocca, P. Contini, M. Mangion, J. Stratton, M. R. Tanda, F. |
| description | 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 |
| doi_str_mv | 10.1093/annonc/mdf326 |
| format | Article |
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F. ; Sarobba, M. G. ; Farris, A. ; Olmeo, N. ; Contu, A. ; Pasca, A. ; Satta, M. P. ; Persico, I. ; Carboni, A. A. ; Cossu-Rocca, P. ; Contini, M. ; Mangion, J. ; Stratton, M. R. ; Tanda, F.</creator><creatorcontrib>Palmieri, G. ; Palomba, G. ; Cossu, A. ; Pisano, M. ; Dedola, M. F. ; Sarobba, M. G. ; Farris, A. ; Olmeo, N. ; Contu, A. ; Pasca, A. ; Satta, M. P. ; Persico, I. ; Carboni, A. A. ; Cossu-Rocca, P. ; Contini, M. ; Mangion, J. ; Stratton, M. R. ; Tanda, F.</creatorcontrib><description>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.</description><identifier>ISSN: 0923-7534</identifier><identifier>EISSN: 1569-8041</identifier><identifier>DOI: 10.1093/annonc/mdf326</identifier><identifier>PMID: 12453858</identifier><language>eng</language><publisher>Oxford: Oxford University Press</publisher><subject>Adult ; Aged ; Biological and medical sciences ; Biomarkers, Tumor - analysis ; breast cancer ; Breast Neoplasms - epidemiology ; Breast Neoplasms - genetics ; Breast Neoplasms, Male - epidemiology ; Breast Neoplasms, Male - genetics ; DNA Mutational Analysis ; Female ; Genes, BRCA1 ; Genes, BRCA2 ; genetic counseling ; Genetic Counseling - standards ; Genetic Counseling - trends ; Genetic Predisposition to Disease ; Genetic Testing ; genetically homogeneous population ; Germ-Line Mutation ; germline mutation ; Gynecology. Andrology. Obstetrics ; Humans ; Incidence ; Italy - epidemiology ; Key words:BRCA1/2 genes ; Male ; Mammary gland diseases ; Medical sciences ; Middle Aged ; Pedigree ; Polymerase Chain Reaction - methods ; polymerase chain reaction-based screening ; Polymorphism, Single-Stranded Conformational ; Population Surveillance ; Risk Factors ; Survival Analysis ; Tumors</subject><ispartof>Annals of oncology, 2002-12, Vol.13 (12), p.1899-1907</ispartof><rights>2003 INIST-CNRS</rights><rights>Copyright Springer Science & Business Media Dec 2002</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c423t-3f53a0798c01e415a7cc6a831cd29cea14bb6c0aaee699d567e53fbf92bccb833</citedby><cites>FETCH-LOGICAL-c423t-3f53a0798c01e415a7cc6a831cd29cea14bb6c0aaee699d567e53fbf92bccb833</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27922,27923</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14414640$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12453858$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Palmieri, G.</creatorcontrib><creatorcontrib>Palomba, G.</creatorcontrib><creatorcontrib>Cossu, A.</creatorcontrib><creatorcontrib>Pisano, M.</creatorcontrib><creatorcontrib>Dedola, M. F.</creatorcontrib><creatorcontrib>Sarobba, M. G.</creatorcontrib><creatorcontrib>Farris, A.</creatorcontrib><creatorcontrib>Olmeo, N.</creatorcontrib><creatorcontrib>Contu, A.</creatorcontrib><creatorcontrib>Pasca, A.</creatorcontrib><creatorcontrib>Satta, M. P.</creatorcontrib><creatorcontrib>Persico, I.</creatorcontrib><creatorcontrib>Carboni, A. A.</creatorcontrib><creatorcontrib>Cossu-Rocca, P.</creatorcontrib><creatorcontrib>Contini, M.</creatorcontrib><creatorcontrib>Mangion, J.</creatorcontrib><creatorcontrib>Stratton, M. R.</creatorcontrib><creatorcontrib>Tanda, F.</creatorcontrib><title>BRCA1 and BRCA2 germline mutations in Sardinian breast cancer families and their implications for genetic counseling</title><title>Annals of oncology</title><addtitle>Ann Oncol</addtitle><description>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.</description><subject>Adult</subject><subject>Aged</subject><subject>Biological and medical sciences</subject><subject>Biomarkers, Tumor - analysis</subject><subject>breast cancer</subject><subject>Breast Neoplasms - epidemiology</subject><subject>Breast Neoplasms - genetics</subject><subject>Breast Neoplasms, Male - epidemiology</subject><subject>Breast Neoplasms, Male - genetics</subject><subject>DNA Mutational Analysis</subject><subject>Female</subject><subject>Genes, BRCA1</subject><subject>Genes, BRCA2</subject><subject>genetic counseling</subject><subject>Genetic Counseling - standards</subject><subject>Genetic Counseling - trends</subject><subject>Genetic Predisposition to Disease</subject><subject>Genetic Testing</subject><subject>genetically homogeneous population</subject><subject>Germ-Line Mutation</subject><subject>germline mutation</subject><subject>Gynecology. Andrology. Obstetrics</subject><subject>Humans</subject><subject>Incidence</subject><subject>Italy - epidemiology</subject><subject>Key words:BRCA1/2 genes</subject><subject>Male</subject><subject>Mammary gland diseases</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Pedigree</subject><subject>Polymerase Chain Reaction - methods</subject><subject>polymerase chain reaction-based screening</subject><subject>Polymorphism, Single-Stranded Conformational</subject><subject>Population Surveillance</subject><subject>Risk Factors</subject><subject>Survival Analysis</subject><subject>Tumors</subject><issn>0923-7534</issn><issn>1569-8041</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkU1rFTEUhoMo9lpdupUg6G5svmeybC9qhdKCHyBuwpnMmZo6k7lNMmD_fed6ByuuEshznhzel5CXnL3jzMoTiHGK_mTseinMI7Lh2tiqYYo_JhtmhaxqLdUReZbzDWPMWGGfkiMulJaNbjaknH3ennIKsaP7m6DXmMYhRKTjXKCEKWYaIv0CqQsxQKRtQsiFeogeE-1hDEPA_EdQfmJINIy7Ifh1tJ_SYoxYgqd-mmPGxX39nDzpYcj4Yj2PybcP779uz6uLq4-ftqcXlVdClkr2WgKrbeMZR8U11N4baCT3nbAegau2NZ4BIBprO21q1LJveyta79tGymPy9uDdpel2xlzcGLLHYYCI05xdLWrBleIL-Po_8GaaU1x2c9was0-LLVB1gHyack7Yu10KI6Q7x5nbd-EOXbhDFwv_apXO7YjdA72GvwBvVgCyh6FPS6YhP3DLZsqofz4OueDvv--QfjlTy1q78-8_nGT68sw2tWPyHrYio2Q</recordid><startdate>20021201</startdate><enddate>20021201</enddate><creator>Palmieri, G.</creator><creator>Palomba, G.</creator><creator>Cossu, A.</creator><creator>Pisano, M.</creator><creator>Dedola, M. F.</creator><creator>Sarobba, M. G.</creator><creator>Farris, A.</creator><creator>Olmeo, N.</creator><creator>Contu, A.</creator><creator>Pasca, A.</creator><creator>Satta, M. P.</creator><creator>Persico, I.</creator><creator>Carboni, A. A.</creator><creator>Cossu-Rocca, P.</creator><creator>Contini, M.</creator><creator>Mangion, J.</creator><creator>Stratton, M. R.</creator><creator>Tanda, F.</creator><general>Oxford University Press</general><general>Oxford Publishing Limited (England)</general><scope>BSCLL</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>7TM</scope><scope>7TO</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope></search><sort><creationdate>20021201</creationdate><title>BRCA1 and BRCA2 germline mutations in Sardinian breast cancer families and their implications for genetic counseling</title><author>Palmieri, G. ; Palomba, G. ; Cossu, A. ; Pisano, M. ; Dedola, M. F. ; Sarobba, M. G. ; Farris, A. ; Olmeo, N. ; Contu, A. ; Pasca, A. ; Satta, M. P. ; Persico, I. ; Carboni, A. A. ; Cossu-Rocca, P. ; Contini, M. ; Mangion, J. ; Stratton, M. R. ; Tanda, F.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c423t-3f53a0798c01e415a7cc6a831cd29cea14bb6c0aaee699d567e53fbf92bccb833</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Biological and medical sciences</topic><topic>Biomarkers, Tumor - analysis</topic><topic>breast cancer</topic><topic>Breast Neoplasms - epidemiology</topic><topic>Breast Neoplasms - genetics</topic><topic>Breast Neoplasms, Male - epidemiology</topic><topic>Breast Neoplasms, Male - genetics</topic><topic>DNA Mutational Analysis</topic><topic>Female</topic><topic>Genes, BRCA1</topic><topic>Genes, BRCA2</topic><topic>genetic counseling</topic><topic>Genetic Counseling - standards</topic><topic>Genetic Counseling - trends</topic><topic>Genetic Predisposition to Disease</topic><topic>Genetic Testing</topic><topic>genetically homogeneous population</topic><topic>Germ-Line Mutation</topic><topic>germline mutation</topic><topic>Gynecology. Andrology. Obstetrics</topic><topic>Humans</topic><topic>Incidence</topic><topic>Italy - epidemiology</topic><topic>Key words:BRCA1/2 genes</topic><topic>Male</topic><topic>Mammary gland diseases</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Pedigree</topic><topic>Polymerase Chain Reaction - methods</topic><topic>polymerase chain reaction-based screening</topic><topic>Polymorphism, Single-Stranded Conformational</topic><topic>Population Surveillance</topic><topic>Risk Factors</topic><topic>Survival Analysis</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Palmieri, G.</creatorcontrib><creatorcontrib>Palomba, G.</creatorcontrib><creatorcontrib>Cossu, A.</creatorcontrib><creatorcontrib>Pisano, M.</creatorcontrib><creatorcontrib>Dedola, M. F.</creatorcontrib><creatorcontrib>Sarobba, M. G.</creatorcontrib><creatorcontrib>Farris, A.</creatorcontrib><creatorcontrib>Olmeo, N.</creatorcontrib><creatorcontrib>Contu, A.</creatorcontrib><creatorcontrib>Pasca, A.</creatorcontrib><creatorcontrib>Satta, M. P.</creatorcontrib><creatorcontrib>Persico, I.</creatorcontrib><creatorcontrib>Carboni, A. A.</creatorcontrib><creatorcontrib>Cossu-Rocca, P.</creatorcontrib><creatorcontrib>Contini, M.</creatorcontrib><creatorcontrib>Mangion, J.</creatorcontrib><creatorcontrib>Stratton, M. R.</creatorcontrib><creatorcontrib>Tanda, F.</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Annals of oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Palmieri, G.</au><au>Palomba, G.</au><au>Cossu, A.</au><au>Pisano, M.</au><au>Dedola, M. F.</au><au>Sarobba, M. G.</au><au>Farris, A.</au><au>Olmeo, N.</au><au>Contu, A.</au><au>Pasca, A.</au><au>Satta, M. P.</au><au>Persico, I.</au><au>Carboni, A. A.</au><au>Cossu-Rocca, P.</au><au>Contini, M.</au><au>Mangion, J.</au><au>Stratton, M. R.</au><au>Tanda, F.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>BRCA1 and BRCA2 germline mutations in Sardinian breast cancer families and their implications for genetic counseling</atitle><jtitle>Annals of oncology</jtitle><addtitle>Ann Oncol</addtitle><date>2002-12-01</date><risdate>2002</risdate><volume>13</volume><issue>12</issue><spage>1899</spage><epage>1907</epage><pages>1899-1907</pages><issn>0923-7534</issn><eissn>1569-8041</eissn><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.</abstract><cop>Oxford</cop><pub>Oxford University Press</pub><pmid>12453858</pmid><doi>10.1093/annonc/mdf326</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Aged Biological and medical sciences Biomarkers, Tumor - analysis breast cancer Breast Neoplasms - epidemiology Breast Neoplasms - genetics Breast Neoplasms, Male - epidemiology Breast Neoplasms, Male - genetics DNA Mutational Analysis Female Genes, BRCA1 Genes, BRCA2 genetic counseling Genetic Counseling - standards Genetic Counseling - trends Genetic Predisposition to Disease Genetic Testing genetically homogeneous population Germ-Line Mutation germline mutation Gynecology. Andrology. Obstetrics Humans Incidence Italy - epidemiology Key words:BRCA1/2 genes Male Mammary gland diseases Medical sciences Middle Aged Pedigree Polymerase Chain Reaction - methods polymerase chain reaction-based screening Polymorphism, Single-Stranded Conformational Population Surveillance Risk Factors Survival Analysis Tumors |
| title | BRCA1 and BRCA2 germline mutations in Sardinian breast cancer families and their implications for genetic counseling |
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