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PALB2 sequencing in Italian familial breast cancer cases reveals a high-risk mutation recurrent in the province of Bergamo
Monoallelic germ-line deleterious mutations of PALB2 (partner and localizer of BRCA2) are associated with breast cancer risk and have been found in several populations, with carrier frequencies of ~1-2%. Initially, these mutations were considered to have moderate penetrance, but accumulating evidenc...
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| Published in: | Genetics in medicine 2014-09, Vol.16 (9), p.688-694 |
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| container_end_page | 694 |
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| container_title | Genetics in medicine |
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| creator | Catucci, Irene Peterlongo, Paolo Ciceri, Sara Colombo, Mara Pasquini, Graziella Barile, Monica Bonanni, Bernardo Verderio, Paolo Pizzamiglio, Sara Foglia, Claudia Falanga, Anna Marchetti, Marina Galastri, Laura Bianchi, Tiziana Corna, Chiara Ravagnani, Fernando Bernard, Loris Fortuzzi, Stefano Sardella, Domenico Scuvera, Giulietta Peissel, Bernard Manoukian, Siranoush Tondini, Carlo Radice, Paolo |
| description | Monoallelic germ-line deleterious mutations of PALB2 (partner and localizer of BRCA2) are associated with breast cancer risk and have been found in several populations, with carrier frequencies of ~1-2%. Initially, these mutations were considered to have moderate penetrance, but accumulating evidence now indicates that they are associated with much higher risk.
In this study, we sequenced the PALB2 coding regions unlinked to BRCA (breast cancer) genes in 575 probands from Italian breast cancer families recruited in Milan.
We found 12 carriers (2.1%) of deleterious mutations, and none of the mutations was found in 784 controls collected in Milan. One of these mutations, the c.1027C>T (p.Gln343X), was found to be recurrent in the province of Bergamo in northern Italy, being detected in 6/113 (5.3%) familial breast cancer cases and 2/477 (0.4%) controls recruited in this area (Fisher's exact test: P < 0.01).
Our data provide confirmatory findings that, in the Italian population also, deleterious mutations of PALB2 are relatively frequent predisposing factors for breast cancer and may be associated with high risk of the disease. |
| doi_str_mv | 10.1038/gim.2014.13 |
| format | article |
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In this study, we sequenced the PALB2 coding regions unlinked to BRCA (breast cancer) genes in 575 probands from Italian breast cancer families recruited in Milan.
We found 12 carriers (2.1%) of deleterious mutations, and none of the mutations was found in 784 controls collected in Milan. One of these mutations, the c.1027C>T (p.Gln343X), was found to be recurrent in the province of Bergamo in northern Italy, being detected in 6/113 (5.3%) familial breast cancer cases and 2/477 (0.4%) controls recruited in this area (Fisher's exact test: P < 0.01).
Our data provide confirmatory findings that, in the Italian population also, deleterious mutations of PALB2 are relatively frequent predisposing factors for breast cancer and may be associated with high risk of the disease.</description><identifier>ISSN: 1098-3600</identifier><identifier>EISSN: 1530-0366</identifier><identifier>DOI: 10.1038/gim.2014.13</identifier><identifier>PMID: 24556926</identifier><language>eng</language><publisher>United States: Elsevier Limited</publisher><subject>Alleles ; Breast cancer ; Breast Neoplasms - diagnosis ; Breast Neoplasms - genetics ; Case-Control Studies ; DNA Mutational Analysis ; Fanconi Anemia Complementation Group N Protein ; Female ; Genetic Predisposition to Disease ; Genotype ; Humans ; Italy ; Mutation ; Nuclear Proteins - genetics ; Polymorphism, Genetic ; Tumor Suppressor Proteins - genetics ; Whites - genetics</subject><ispartof>Genetics in medicine, 2014-09, Vol.16 (9), p.688-694</ispartof><rights>American College of Medical Genetics and Genomics 2014.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c453t-101adf517abde5bd3296ed8c2a6640097dac96c1599fa4867f42f9e6edee97783</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,786,790,27957,27958</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24556926$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Catucci, Irene</creatorcontrib><creatorcontrib>Peterlongo, Paolo</creatorcontrib><creatorcontrib>Ciceri, Sara</creatorcontrib><creatorcontrib>Colombo, Mara</creatorcontrib><creatorcontrib>Pasquini, Graziella</creatorcontrib><creatorcontrib>Barile, Monica</creatorcontrib><creatorcontrib>Bonanni, Bernardo</creatorcontrib><creatorcontrib>Verderio, Paolo</creatorcontrib><creatorcontrib>Pizzamiglio, Sara</creatorcontrib><creatorcontrib>Foglia, Claudia</creatorcontrib><creatorcontrib>Falanga, Anna</creatorcontrib><creatorcontrib>Marchetti, Marina</creatorcontrib><creatorcontrib>Galastri, Laura</creatorcontrib><creatorcontrib>Bianchi, Tiziana</creatorcontrib><creatorcontrib>Corna, Chiara</creatorcontrib><creatorcontrib>Ravagnani, Fernando</creatorcontrib><creatorcontrib>Bernard, Loris</creatorcontrib><creatorcontrib>Fortuzzi, Stefano</creatorcontrib><creatorcontrib>Sardella, Domenico</creatorcontrib><creatorcontrib>Scuvera, Giulietta</creatorcontrib><creatorcontrib>Peissel, Bernard</creatorcontrib><creatorcontrib>Manoukian, Siranoush</creatorcontrib><creatorcontrib>Tondini, Carlo</creatorcontrib><creatorcontrib>Radice, Paolo</creatorcontrib><title>PALB2 sequencing in Italian familial breast cancer cases reveals a high-risk mutation recurrent in the province of Bergamo</title><title>Genetics in medicine</title><addtitle>Genet Med</addtitle><description>Monoallelic germ-line deleterious mutations of PALB2 (partner and localizer of BRCA2) are associated with breast cancer risk and have been found in several populations, with carrier frequencies of ~1-2%. Initially, these mutations were considered to have moderate penetrance, but accumulating evidence now indicates that they are associated with much higher risk.
In this study, we sequenced the PALB2 coding regions unlinked to BRCA (breast cancer) genes in 575 probands from Italian breast cancer families recruited in Milan.
We found 12 carriers (2.1%) of deleterious mutations, and none of the mutations was found in 784 controls collected in Milan. One of these mutations, the c.1027C>T (p.Gln343X), was found to be recurrent in the province of Bergamo in northern Italy, being detected in 6/113 (5.3%) familial breast cancer cases and 2/477 (0.4%) controls recruited in this area (Fisher's exact test: P < 0.01).
Our data provide confirmatory findings that, in the Italian population also, deleterious mutations of PALB2 are relatively frequent predisposing factors for breast cancer and may be associated with high risk of the disease.</description><subject>Alleles</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - diagnosis</subject><subject>Breast Neoplasms - genetics</subject><subject>Case-Control Studies</subject><subject>DNA Mutational Analysis</subject><subject>Fanconi Anemia Complementation Group N Protein</subject><subject>Female</subject><subject>Genetic Predisposition to Disease</subject><subject>Genotype</subject><subject>Humans</subject><subject>Italy</subject><subject>Mutation</subject><subject>Nuclear Proteins - genetics</subject><subject>Polymorphism, Genetic</subject><subject>Tumor Suppressor Proteins - genetics</subject><subject>Whites - genetics</subject><issn>1098-3600</issn><issn>1530-0366</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><recordid>eNqFkb1vFDEQxS1ERMKFih5ZokFCe3js9VeZRAmJdBIUpLZ83tk7h11vsHcjwV8fnxIo0lDNSPObp3nzCHkPbA1MmC-7OK45g3YN4hU5ASlYw4RSr2vPrGmEYuyYvC3ljjHQgrM35Ji3UirL1Qn58_1sc85pwV8LphDTjsZEb2Y_RJ9o78dYm4FuM_oy0-BTwFxLwUIzPqAfCvV0H3f7Jsfyk47L7Oc4pToMS86Y5oPcvEd6n6eHWLfp1NNzzDs_TqfkqK8C-O65rsjt1eWPi-tm8-3rzcXZpgmtFHMDDHzXS9B-26HcdoJbhZ0J3CvVMmZ154NVAaS1vW-N0n3Le4uVQbRaG7Ein5506w3VZZndGEvAYfAJp6U4UIa10hjO_49KBcClqX9ckY8v0LtpyakacdwYrUGDPFCfn6iQp1Iy9u4-x9Hn3w6YO6TnanrukJ4DUekPz5rLdsTuH_s3LvEIYqyVHw</recordid><startdate>20140901</startdate><enddate>20140901</enddate><creator>Catucci, Irene</creator><creator>Peterlongo, Paolo</creator><creator>Ciceri, Sara</creator><creator>Colombo, Mara</creator><creator>Pasquini, Graziella</creator><creator>Barile, Monica</creator><creator>Bonanni, Bernardo</creator><creator>Verderio, Paolo</creator><creator>Pizzamiglio, Sara</creator><creator>Foglia, Claudia</creator><creator>Falanga, Anna</creator><creator>Marchetti, Marina</creator><creator>Galastri, Laura</creator><creator>Bianchi, Tiziana</creator><creator>Corna, Chiara</creator><creator>Ravagnani, Fernando</creator><creator>Bernard, Loris</creator><creator>Fortuzzi, Stefano</creator><creator>Sardella, Domenico</creator><creator>Scuvera, Giulietta</creator><creator>Peissel, Bernard</creator><creator>Manoukian, Siranoush</creator><creator>Tondini, Carlo</creator><creator>Radice, Paolo</creator><general>Elsevier Limited</general><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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>20140901</creationdate><title>PALB2 sequencing in Italian familial breast cancer cases reveals a high-risk mutation recurrent in the province of Bergamo</title><author>Catucci, Irene ; Peterlongo, Paolo ; Ciceri, Sara ; Colombo, Mara ; Pasquini, Graziella ; Barile, Monica ; Bonanni, Bernardo ; Verderio, Paolo ; Pizzamiglio, Sara ; Foglia, Claudia ; Falanga, Anna ; Marchetti, Marina ; Galastri, Laura ; Bianchi, Tiziana ; Corna, Chiara ; Ravagnani, Fernando ; Bernard, Loris ; Fortuzzi, Stefano ; Sardella, Domenico ; Scuvera, Giulietta ; Peissel, Bernard ; Manoukian, Siranoush ; Tondini, Carlo ; Radice, Paolo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c453t-101adf517abde5bd3296ed8c2a6640097dac96c1599fa4867f42f9e6edee97783</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Alleles</topic><topic>Breast cancer</topic><topic>Breast Neoplasms - 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Initially, these mutations were considered to have moderate penetrance, but accumulating evidence now indicates that they are associated with much higher risk.
In this study, we sequenced the PALB2 coding regions unlinked to BRCA (breast cancer) genes in 575 probands from Italian breast cancer families recruited in Milan.
We found 12 carriers (2.1%) of deleterious mutations, and none of the mutations was found in 784 controls collected in Milan. One of these mutations, the c.1027C>T (p.Gln343X), was found to be recurrent in the province of Bergamo in northern Italy, being detected in 6/113 (5.3%) familial breast cancer cases and 2/477 (0.4%) controls recruited in this area (Fisher's exact test: P < 0.01).
Our data provide confirmatory findings that, in the Italian population also, deleterious mutations of PALB2 are relatively frequent predisposing factors for breast cancer and may be associated with high risk of the disease.</abstract><cop>United States</cop><pub>Elsevier Limited</pub><pmid>24556926</pmid><doi>10.1038/gim.2014.13</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Genetics in medicine, 2014-09, Vol.16 (9), p.688-694 |
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| source | ScienceDirect® |
| subjects | Alleles Breast cancer Breast Neoplasms - diagnosis Breast Neoplasms - genetics Case-Control Studies DNA Mutational Analysis Fanconi Anemia Complementation Group N Protein Female Genetic Predisposition to Disease Genotype Humans Italy Mutation Nuclear Proteins - genetics Polymorphism, Genetic Tumor Suppressor Proteins - genetics Whites - genetics |
| title | PALB2 sequencing in Italian familial breast cancer cases reveals a high-risk mutation recurrent in the province of Bergamo |
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