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Mismatch repair gene pathogenic germline variants in a population-based cohort of breast cancer
The advent of gene panel testing is challenging the previous practice of using clinically defined cancer family syndromes to inform single-gene genetic screening. Individual and family cancer histories that would have previously indicated testing of a single gene or a small number of related genes a...
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| Published in: | Familial cancer 2020-07, Vol.19 (3), p.197-202 |
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| container_end_page | 202 |
| container_issue | 3 |
| container_start_page | 197 |
| container_title | Familial cancer |
| container_volume | 19 |
| creator | Nguyen-Dumont, Tu Steen, Jason A. Winship, Ingrid Park, Daniel J. Pope, Bernard J. Hammet, Fleur Mahmoodi, Maryam Tsimiklis, Helen Theys, Derrick Clendenning, Mark Giles, Graham G. Hopper, John L. Southey, Melissa C. |
| description | The advent of gene panel testing is challenging the previous practice of using clinically defined cancer family syndromes to inform single-gene genetic screening. Individual and family cancer histories that would have previously indicated testing of a single gene or a small number of related genes are now, increasingly, leading to screening across gene panels that contain larger numbers of genes. We have applied a gene panel test that included four DNA mismatch repair (MMR) genes (
MLH1
,
MSH2
,
MSH6
and
PMS2
) to an Australian population-based case–control-family study of breast cancer. Altogether, eight pathogenic variants in MMR genes were identified: six in 1421 case-families (0.4%, 4
MSH6
and 2
PMS2
) and two in 833 control-families (0.2%, one each of
MLH1
and
MSH2
). This testing highlights the current and future challenges for clinical genetics in the context of anticipated gene panel-based population-based screening that includes the MMR genes. This testing is likely to provide additional opportunities for cancer prevention via cascade testing for Lynch syndrome and precision medicine for breast cancer treatment. |
| doi_str_mv | 10.1007/s10689-020-00164-7 |
| format | article |
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MLH1
,
MSH2
,
MSH6
and
PMS2
) to an Australian population-based case–control-family study of breast cancer. Altogether, eight pathogenic variants in MMR genes were identified: six in 1421 case-families (0.4%, 4
MSH6
and 2
PMS2
) and two in 833 control-families (0.2%, one each of
MLH1
and
MSH2
). This testing highlights the current and future challenges for clinical genetics in the context of anticipated gene panel-based population-based screening that includes the MMR genes. This testing is likely to provide additional opportunities for cancer prevention via cascade testing for Lynch syndrome and precision medicine for breast cancer treatment.</description><identifier>ISSN: 1389-9600</identifier><identifier>ISSN: 1573-7292</identifier><identifier>EISSN: 1573-7292</identifier><identifier>DOI: 10.1007/s10689-020-00164-7</identifier><identifier>PMID: 32060697</identifier><language>eng</language><publisher>Dordrecht: Springer Netherlands</publisher><subject>Biomedical and Life Sciences ; Biomedicine ; Breast cancer ; Breast Neoplasms - genetics ; Cancer Research ; Case-Control Studies ; Cohort Studies ; Colorectal cancer ; Colorectal Neoplasms, Hereditary Nonpolyposis - genetics ; DNA Mismatch Repair - genetics ; DNA repair ; DNA-Binding Proteins - genetics ; Epidemiology ; Female ; Gene Expression Profiling - methods ; Genes ; Genetic disorders ; Genetic Predisposition to Disease ; Genetic screening ; Germ-Line Mutation ; Human Genetics ; Humans ; Mismatch repair ; Mismatch Repair Endonuclease PMS2 - genetics ; MLH1 protein ; MSH2 protein ; MSH6 protein ; MutL Protein Homolog 1 - genetics ; MutS Homolog 2 Protein - genetics ; New South Wales ; Pedigree ; Population studies ; Precision medicine ; Registries - statistics & numerical data ; Short Communication ; Victoria ; Yeast</subject><ispartof>Familial cancer, 2020-07, Vol.19 (3), p.197-202</ispartof><rights>Springer Nature B.V. 2020</rights><rights>Springer Nature B.V. 2020.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c375t-955d0a32da1dbeb83df50ec83e24f95517272daf385483a21d2859279a0b187c3</citedby><cites>FETCH-LOGICAL-c375t-955d0a32da1dbeb83df50ec83e24f95517272daf385483a21d2859279a0b187c3</cites><orcidid>0000-0001-9852-2103 ; 0000-0002-6217-0182 ; 0000-0002-6354-0931 ; 0000-0003-4946-9099 ; 0000-0002-4840-1095 ; 0000-0002-6313-9005 ; 0000-0001-8535-6003</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32060697$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Nguyen-Dumont, Tu</creatorcontrib><creatorcontrib>Steen, Jason A.</creatorcontrib><creatorcontrib>Winship, Ingrid</creatorcontrib><creatorcontrib>Park, Daniel J.</creatorcontrib><creatorcontrib>Pope, Bernard J.</creatorcontrib><creatorcontrib>Hammet, Fleur</creatorcontrib><creatorcontrib>Mahmoodi, Maryam</creatorcontrib><creatorcontrib>Tsimiklis, Helen</creatorcontrib><creatorcontrib>Theys, Derrick</creatorcontrib><creatorcontrib>Clendenning, Mark</creatorcontrib><creatorcontrib>Giles, Graham G.</creatorcontrib><creatorcontrib>Hopper, John L.</creatorcontrib><creatorcontrib>Southey, Melissa C.</creatorcontrib><title>Mismatch repair gene pathogenic germline variants in a population-based cohort of breast cancer</title><title>Familial cancer</title><addtitle>Familial Cancer</addtitle><addtitle>Fam Cancer</addtitle><description>The advent of gene panel testing is challenging the previous practice of using clinically defined cancer family syndromes to inform single-gene genetic screening. Individual and family cancer histories that would have previously indicated testing of a single gene or a small number of related genes are now, increasingly, leading to screening across gene panels that contain larger numbers of genes. We have applied a gene panel test that included four DNA mismatch repair (MMR) genes (
MLH1
,
MSH2
,
MSH6
and
PMS2
) to an Australian population-based case–control-family study of breast cancer. Altogether, eight pathogenic variants in MMR genes were identified: six in 1421 case-families (0.4%, 4
MSH6
and 2
PMS2
) and two in 833 control-families (0.2%, one each of
MLH1
and
MSH2
). This testing highlights the current and future challenges for clinical genetics in the context of anticipated gene panel-based population-based screening that includes the MMR genes. This testing is likely to provide additional opportunities for cancer prevention via cascade testing for Lynch syndrome and precision medicine for breast cancer treatment.</description><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - genetics</subject><subject>Cancer Research</subject><subject>Case-Control Studies</subject><subject>Cohort Studies</subject><subject>Colorectal cancer</subject><subject>Colorectal Neoplasms, Hereditary Nonpolyposis - genetics</subject><subject>DNA Mismatch Repair - genetics</subject><subject>DNA repair</subject><subject>DNA-Binding Proteins - genetics</subject><subject>Epidemiology</subject><subject>Female</subject><subject>Gene Expression Profiling - methods</subject><subject>Genes</subject><subject>Genetic disorders</subject><subject>Genetic Predisposition to Disease</subject><subject>Genetic screening</subject><subject>Germ-Line Mutation</subject><subject>Human Genetics</subject><subject>Humans</subject><subject>Mismatch repair</subject><subject>Mismatch Repair Endonuclease PMS2 - genetics</subject><subject>MLH1 protein</subject><subject>MSH2 protein</subject><subject>MSH6 protein</subject><subject>MutL Protein Homolog 1 - genetics</subject><subject>MutS Homolog 2 Protein - genetics</subject><subject>New South Wales</subject><subject>Pedigree</subject><subject>Population studies</subject><subject>Precision medicine</subject><subject>Registries - statistics & numerical data</subject><subject>Short Communication</subject><subject>Victoria</subject><subject>Yeast</subject><issn>1389-9600</issn><issn>1573-7292</issn><issn>1573-7292</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNp9kMFu1DAQhi3Uim0LL9BDZakXLoGxHcfxEVWFIhX1Us7WxHFYr5I42AlS356BLSBx4OSx_29mrI-xSwFvBYB5VwQ0ra1AQgUgmroyL9iZ0EZVRlp5QrWi2DYAO3ZeygGIlMq8ZDsloYHGmjPmPscy4er3PIcFY-Zfwxz4gus-URU93fM0Rnr7jjnivBYeZ458Scs24hrTXHVYQs992qe88jTwLgcsK_c4-5BfsdMBxxJeP58X7MuH28ebu-r-4eOnm_f3lVdGr5XVugdUskfRd6FrVT9oCL5VQdYDhcJIQ-GgWl23CqXoZautNBahE63x6oK9Oc5dcvq2hbK6KRYfxhHnkLbipNLaqlZpIPT6H_SQtjzT75ysQde0rLFEySPlcyolh8EtOU6Yn5wA91O_O-p3JNX90u8MNV09j966KfR_Wn77JkAdgULRTG7_7v7P2B_mHI-Y</recordid><startdate>20200701</startdate><enddate>20200701</enddate><creator>Nguyen-Dumont, Tu</creator><creator>Steen, Jason A.</creator><creator>Winship, Ingrid</creator><creator>Park, Daniel J.</creator><creator>Pope, Bernard J.</creator><creator>Hammet, Fleur</creator><creator>Mahmoodi, Maryam</creator><creator>Tsimiklis, Helen</creator><creator>Theys, Derrick</creator><creator>Clendenning, Mark</creator><creator>Giles, Graham G.</creator><creator>Hopper, John L.</creator><creator>Southey, Melissa C.</creator><general>Springer Netherlands</general><general>Springer Nature B.V</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>8AO</scope><scope>8FD</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K9-</scope><scope>K9.</scope><scope>M0R</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-9852-2103</orcidid><orcidid>https://orcid.org/0000-0002-6217-0182</orcidid><orcidid>https://orcid.org/0000-0002-6354-0931</orcidid><orcidid>https://orcid.org/0000-0003-4946-9099</orcidid><orcidid>https://orcid.org/0000-0002-4840-1095</orcidid><orcidid>https://orcid.org/0000-0002-6313-9005</orcidid><orcidid>https://orcid.org/0000-0001-8535-6003</orcidid></search><sort><creationdate>20200701</creationdate><title>Mismatch repair gene pathogenic germline variants in a population-based cohort of breast cancer</title><author>Nguyen-Dumont, Tu ; Steen, Jason A. ; Winship, Ingrid ; Park, Daniel J. ; Pope, Bernard J. ; Hammet, Fleur ; Mahmoodi, Maryam ; Tsimiklis, Helen ; Theys, Derrick ; Clendenning, Mark ; Giles, Graham G. ; Hopper, John L. ; Southey, Melissa C.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c375t-955d0a32da1dbeb83df50ec83e24f95517272daf385483a21d2859279a0b187c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Breast cancer</topic><topic>Breast Neoplasms - genetics</topic><topic>Cancer Research</topic><topic>Case-Control Studies</topic><topic>Cohort Studies</topic><topic>Colorectal cancer</topic><topic>Colorectal Neoplasms, Hereditary Nonpolyposis - genetics</topic><topic>DNA Mismatch Repair - genetics</topic><topic>DNA repair</topic><topic>DNA-Binding Proteins - genetics</topic><topic>Epidemiology</topic><topic>Female</topic><topic>Gene Expression Profiling - methods</topic><topic>Genes</topic><topic>Genetic disorders</topic><topic>Genetic Predisposition to Disease</topic><topic>Genetic screening</topic><topic>Germ-Line Mutation</topic><topic>Human Genetics</topic><topic>Humans</topic><topic>Mismatch repair</topic><topic>Mismatch Repair Endonuclease PMS2 - genetics</topic><topic>MLH1 protein</topic><topic>MSH2 protein</topic><topic>MSH6 protein</topic><topic>MutL Protein Homolog 1 - genetics</topic><topic>MutS Homolog 2 Protein - genetics</topic><topic>New South Wales</topic><topic>Pedigree</topic><topic>Population studies</topic><topic>Precision medicine</topic><topic>Registries - statistics & numerical data</topic><topic>Short Communication</topic><topic>Victoria</topic><topic>Yeast</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Nguyen-Dumont, Tu</creatorcontrib><creatorcontrib>Steen, Jason A.</creatorcontrib><creatorcontrib>Winship, Ingrid</creatorcontrib><creatorcontrib>Park, Daniel J.</creatorcontrib><creatorcontrib>Pope, Bernard J.</creatorcontrib><creatorcontrib>Hammet, Fleur</creatorcontrib><creatorcontrib>Mahmoodi, Maryam</creatorcontrib><creatorcontrib>Tsimiklis, Helen</creatorcontrib><creatorcontrib>Theys, Derrick</creatorcontrib><creatorcontrib>Clendenning, Mark</creatorcontrib><creatorcontrib>Giles, Graham G.</creatorcontrib><creatorcontrib>Hopper, John L.</creatorcontrib><creatorcontrib>Southey, Melissa C.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>ProQuest Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>Consumer Health Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Family Health Database (ProQuest)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>ProQuest research library</collection><collection>Research Library (Corporate)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Familial cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Nguyen-Dumont, Tu</au><au>Steen, Jason A.</au><au>Winship, Ingrid</au><au>Park, Daniel J.</au><au>Pope, Bernard J.</au><au>Hammet, Fleur</au><au>Mahmoodi, Maryam</au><au>Tsimiklis, Helen</au><au>Theys, Derrick</au><au>Clendenning, Mark</au><au>Giles, Graham G.</au><au>Hopper, John L.</au><au>Southey, Melissa C.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mismatch repair gene pathogenic germline variants in a population-based cohort of breast cancer</atitle><jtitle>Familial cancer</jtitle><stitle>Familial Cancer</stitle><addtitle>Fam Cancer</addtitle><date>2020-07-01</date><risdate>2020</risdate><volume>19</volume><issue>3</issue><spage>197</spage><epage>202</epage><pages>197-202</pages><issn>1389-9600</issn><issn>1573-7292</issn><eissn>1573-7292</eissn><abstract>The advent of gene panel testing is challenging the previous practice of using clinically defined cancer family syndromes to inform single-gene genetic screening. Individual and family cancer histories that would have previously indicated testing of a single gene or a small number of related genes are now, increasingly, leading to screening across gene panels that contain larger numbers of genes. We have applied a gene panel test that included four DNA mismatch repair (MMR) genes (
MLH1
,
MSH2
,
MSH6
and
PMS2
) to an Australian population-based case–control-family study of breast cancer. Altogether, eight pathogenic variants in MMR genes were identified: six in 1421 case-families (0.4%, 4
MSH6
and 2
PMS2
) and two in 833 control-families (0.2%, one each of
MLH1
and
MSH2
). This testing highlights the current and future challenges for clinical genetics in the context of anticipated gene panel-based population-based screening that includes the MMR genes. This testing is likely to provide additional opportunities for cancer prevention via cascade testing for Lynch syndrome and precision medicine for breast cancer treatment.</abstract><cop>Dordrecht</cop><pub>Springer Netherlands</pub><pmid>32060697</pmid><doi>10.1007/s10689-020-00164-7</doi><tpages>6</tpages><orcidid>https://orcid.org/0000-0001-9852-2103</orcidid><orcidid>https://orcid.org/0000-0002-6217-0182</orcidid><orcidid>https://orcid.org/0000-0002-6354-0931</orcidid><orcidid>https://orcid.org/0000-0003-4946-9099</orcidid><orcidid>https://orcid.org/0000-0002-4840-1095</orcidid><orcidid>https://orcid.org/0000-0002-6313-9005</orcidid><orcidid>https://orcid.org/0000-0001-8535-6003</orcidid></addata></record> |
| fulltext | fulltext |
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| ispartof | Familial cancer, 2020-07, Vol.19 (3), p.197-202 |
| issn | 1389-9600 1573-7292 1573-7292 |
| language | eng |
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| subjects | Biomedical and Life Sciences Biomedicine Breast cancer Breast Neoplasms - genetics Cancer Research Case-Control Studies Cohort Studies Colorectal cancer Colorectal Neoplasms, Hereditary Nonpolyposis - genetics DNA Mismatch Repair - genetics DNA repair DNA-Binding Proteins - genetics Epidemiology Female Gene Expression Profiling - methods Genes Genetic disorders Genetic Predisposition to Disease Genetic screening Germ-Line Mutation Human Genetics Humans Mismatch repair Mismatch Repair Endonuclease PMS2 - genetics MLH1 protein MSH2 protein MSH6 protein MutL Protein Homolog 1 - genetics MutS Homolog 2 Protein - genetics New South Wales Pedigree Population studies Precision medicine Registries - statistics & numerical data Short Communication Victoria Yeast |
| title | Mismatch repair gene pathogenic germline variants in a population-based cohort of breast cancer |
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