Age‐dependent performance of BRAF mutation testing in Lynch syndrome diagnostics
BRAF V600E mutations have been reported as a marker of sporadic microsatellite instability (MSI) colorectal cancer (CRC). Current international diagnostic guidelines recommend BRAF mutation testing in MSI CRC patients to predict low risk of Lynch syndrome (LS). We evaluated the age‐specific performa...
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| creator | Bläker, Hendrik Haupt, Saskia Morak, Monika Holinski‐Feder, Elke Arnold, Alexander Horst, David Sieber‐Frank, Julia Seidler, Florian Winterfeld, Moritz Alwers, Elizabeth Chang‐Claude, Jenny Brenner, Hermann Roth, Wilfried Engel, Christoph Löffler, Markus Möslein, Gabriela Schackert, Hans‐Konrad Weitz, Jürgen Perne, Claudia Aretz, Stefan Hüneburg, Robert Schmiegel, Wolff Vangala, Deepak Rahner, Nils Steinke‐Lange, Verena Heuveline, Vincent von Knebel Doeberitz, Magnus Ahadova, Aysel Hoffmeister, Michael Kloor, Matthias |
| description | BRAF V600E mutations have been reported as a marker of sporadic microsatellite instability (MSI) colorectal cancer (CRC). Current international diagnostic guidelines recommend BRAF mutation testing in MSI CRC patients to predict low risk of Lynch syndrome (LS). We evaluated the age‐specific performance of BRAF testing in LS diagnostics. We systematically compared the prevalence of BRAF mutations in LS‐associated CRCs and unselected MSI CRCs in different age groups as available from published studies, databases and population‐based patient cohorts. Sensitivity/specificity analysis of BRAF testing for exclusion of LS and cost calculations were performed. Among 969 MSI CRCs from LS carriers in the literature and German HNPCC Consortium, 15 (1.6%) harbored BRAF mutations. Six of seven LS patients with BRAF‐mutant CRC and reported age were |
| doi_str_mv | 10.1002/ijc.33273 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_journals_2445257141</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2445257141</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3883-ef4d322f26cfa1ad0215655763562e69836585eac4e2af3fee2b969da33aa8533</originalsourceid><addsrcrecordid>eNp1kL1OwzAUhS0EoqUw8ALIEhNDWv_ETjKWikJRJaQKZsuNr0uqxglOIpSNR-AZeRJSUtiY7nA-fffoIHRJyZgSwibZNh1zziJ-hIaUJFFAGBXHaNhlJIgolwN0VlVbQigVJDxFA87iSAjBh2g13cDXx6eBEpwBV-MSvC18rl0KuLD4djWd47ypdZ0VDtdQ1Znb4MzhZevSV1y1zvgiB2wyvXFFl6bVOTqxelfBxeGO0Mv87nn2ECyf7hez6TJIeRzzAGxoOGOWydRqqs2-sxQiklxIBjKJuRSxAJ2GwLTlFoCtE5kYzbnWseB8hK57b-mLt6ZrprZF4133UrEwFExENKQdddNTqS-qyoNVpc9y7VtFidqvp7r11M96HXt1MDbrHMwf-TtXB0x64D3bQfu_SS0eZ73yG8v1eUc</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2445257141</pqid></control><display><type>article</type><title>Age‐dependent performance of BRAF mutation testing in Lynch syndrome diagnostics</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><source>EZB-FREE-00999 freely available EZB journals</source><creator>Bläker, Hendrik ; Haupt, Saskia ; Morak, Monika ; Holinski‐Feder, Elke ; Arnold, Alexander ; Horst, David ; Sieber‐Frank, Julia ; Seidler, Florian ; Winterfeld, Moritz ; Alwers, Elizabeth ; Chang‐Claude, Jenny ; Brenner, Hermann ; Roth, Wilfried ; Engel, Christoph ; Löffler, Markus ; Möslein, Gabriela ; Schackert, Hans‐Konrad ; Weitz, Jürgen ; Perne, Claudia ; Aretz, Stefan ; Hüneburg, Robert ; Schmiegel, Wolff ; Vangala, Deepak ; Rahner, Nils ; Steinke‐Lange, Verena ; Heuveline, Vincent ; von Knebel Doeberitz, Magnus ; Ahadova, Aysel ; Hoffmeister, Michael ; Kloor, Matthias</creator><creatorcontrib>Bläker, Hendrik ; Haupt, Saskia ; Morak, Monika ; Holinski‐Feder, Elke ; Arnold, Alexander ; Horst, David ; Sieber‐Frank, Julia ; Seidler, Florian ; Winterfeld, Moritz ; Alwers, Elizabeth ; Chang‐Claude, Jenny ; Brenner, Hermann ; Roth, Wilfried ; Engel, Christoph ; Löffler, Markus ; Möslein, Gabriela ; Schackert, Hans‐Konrad ; Weitz, Jürgen ; Perne, Claudia ; Aretz, Stefan ; Hüneburg, Robert ; Schmiegel, Wolff ; Vangala, Deepak ; Rahner, Nils ; Steinke‐Lange, Verena ; Heuveline, Vincent ; von Knebel Doeberitz, Magnus ; Ahadova, Aysel ; Hoffmeister, Michael ; Kloor, Matthias ; German Consortium for Familial Intestinal Cancer ; The German Consortium for Familial Intestinal Cancer</creatorcontrib><description>BRAF V600E mutations have been reported as a marker of sporadic microsatellite instability (MSI) colorectal cancer (CRC). Current international diagnostic guidelines recommend BRAF mutation testing in MSI CRC patients to predict low risk of Lynch syndrome (LS). We evaluated the age‐specific performance of BRAF testing in LS diagnostics. We systematically compared the prevalence of BRAF mutations in LS‐associated CRCs and unselected MSI CRCs in different age groups as available from published studies, databases and population‐based patient cohorts. Sensitivity/specificity analysis of BRAF testing for exclusion of LS and cost calculations were performed. Among 969 MSI CRCs from LS carriers in the literature and German HNPCC Consortium, 15 (1.6%) harbored BRAF mutations. Six of seven LS patients with BRAF‐mutant CRC and reported age were <50 years. Among 339 of 756 (44.8%) of BRAF mutations detected in unselected MSI CRC, only 2 of 339 (0.6%) BRAF mutations were detected in patients <50 years. The inclusion of BRAF testing led to high risk of missing LS patients and increased costs at age <50 years. BRAF testing in patients <50 years carries a high risk of missing a hereditary cancer predisposition and is cost‐inefficient. We suggest direct referral of MSI CRC patients <50 years to genetic counseling without BRAF testing.
What's new?
Lynch syndrome (LS) is the most common hereditary colorectal cancer. While these cancers usually show microsatellite instability (MSI), most MSI tumors are sporadic. Here, the authors evaluated the usefulness of testing for BRAF mutations as a way to distinguish LS cancers from sporadic cases. They found that the frequency of tumors carrying BRAF mutations in LS patients under age 50 is very similar to the frequency of those mutations in MSI cancers from that age group, suggesting that there's substantial overlap between the two groups. Thus, BRAF mutation status should not be used to exclude LS in patients under 50.</description><identifier>ISSN: 0020-7136</identifier><identifier>EISSN: 1097-0215</identifier><identifier>DOI: 10.1002/ijc.33273</identifier><identifier>PMID: 32875553</identifier><language>eng</language><publisher>Hoboken, USA: John Wiley & Sons, Inc</publisher><subject>Age ; Age Factors ; Aged ; Amino Acid Substitution ; BRAF mutation testing ; Cancer ; Colorectal cancer ; Colorectal carcinoma ; Colorectal Neoplasms, Hereditary Nonpolyposis - diagnosis ; Colorectal Neoplasms, Hereditary Nonpolyposis - genetics ; Early Detection of Cancer - methods ; Female ; Genetic counseling ; Genetic disorders ; Genetic Markers ; hereditary cancer syndrome ; Humans ; Lynch syndrome diagnostics ; Male ; Medical research ; Microsatellite Instability ; microsatellite instability colorectal cancer ; Middle Aged ; Mutation ; Mutation Rate ; Population studies ; Proto-Oncogene Proteins B-raf - genetics ; Sensitivity and Specificity</subject><ispartof>International journal of cancer, 2020-11, Vol.147 (10), p.2801-2810</ispartof><rights>2020 The Authors. published by John Wiley & Sons Ltd on behalf of Union for International Cancer Control.</rights><rights>2020 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of Union for International Cancer Control.</rights><rights>2020. This article is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3883-ef4d322f26cfa1ad0215655763562e69836585eac4e2af3fee2b969da33aa8533</citedby><cites>FETCH-LOGICAL-c3883-ef4d322f26cfa1ad0215655763562e69836585eac4e2af3fee2b969da33aa8533</cites><orcidid>0000-0001-8491-3234 ; 0000-0001-9890-0450 ; 0000-0002-7247-282X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fijc.33273$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fijc.33273$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32875553$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bläker, Hendrik</creatorcontrib><creatorcontrib>Haupt, Saskia</creatorcontrib><creatorcontrib>Morak, Monika</creatorcontrib><creatorcontrib>Holinski‐Feder, Elke</creatorcontrib><creatorcontrib>Arnold, Alexander</creatorcontrib><creatorcontrib>Horst, David</creatorcontrib><creatorcontrib>Sieber‐Frank, Julia</creatorcontrib><creatorcontrib>Seidler, Florian</creatorcontrib><creatorcontrib>Winterfeld, Moritz</creatorcontrib><creatorcontrib>Alwers, Elizabeth</creatorcontrib><creatorcontrib>Chang‐Claude, Jenny</creatorcontrib><creatorcontrib>Brenner, Hermann</creatorcontrib><creatorcontrib>Roth, Wilfried</creatorcontrib><creatorcontrib>Engel, Christoph</creatorcontrib><creatorcontrib>Löffler, Markus</creatorcontrib><creatorcontrib>Möslein, Gabriela</creatorcontrib><creatorcontrib>Schackert, Hans‐Konrad</creatorcontrib><creatorcontrib>Weitz, Jürgen</creatorcontrib><creatorcontrib>Perne, Claudia</creatorcontrib><creatorcontrib>Aretz, Stefan</creatorcontrib><creatorcontrib>Hüneburg, Robert</creatorcontrib><creatorcontrib>Schmiegel, Wolff</creatorcontrib><creatorcontrib>Vangala, Deepak</creatorcontrib><creatorcontrib>Rahner, Nils</creatorcontrib><creatorcontrib>Steinke‐Lange, Verena</creatorcontrib><creatorcontrib>Heuveline, Vincent</creatorcontrib><creatorcontrib>von Knebel Doeberitz, Magnus</creatorcontrib><creatorcontrib>Ahadova, Aysel</creatorcontrib><creatorcontrib>Hoffmeister, Michael</creatorcontrib><creatorcontrib>Kloor, Matthias</creatorcontrib><creatorcontrib>German Consortium for Familial Intestinal Cancer</creatorcontrib><creatorcontrib>The German Consortium for Familial Intestinal Cancer</creatorcontrib><title>Age‐dependent performance of BRAF mutation testing in Lynch syndrome diagnostics</title><title>International journal of cancer</title><addtitle>Int J Cancer</addtitle><description>BRAF V600E mutations have been reported as a marker of sporadic microsatellite instability (MSI) colorectal cancer (CRC). Current international diagnostic guidelines recommend BRAF mutation testing in MSI CRC patients to predict low risk of Lynch syndrome (LS). We evaluated the age‐specific performance of BRAF testing in LS diagnostics. We systematically compared the prevalence of BRAF mutations in LS‐associated CRCs and unselected MSI CRCs in different age groups as available from published studies, databases and population‐based patient cohorts. Sensitivity/specificity analysis of BRAF testing for exclusion of LS and cost calculations were performed. Among 969 MSI CRCs from LS carriers in the literature and German HNPCC Consortium, 15 (1.6%) harbored BRAF mutations. Six of seven LS patients with BRAF‐mutant CRC and reported age were <50 years. Among 339 of 756 (44.8%) of BRAF mutations detected in unselected MSI CRC, only 2 of 339 (0.6%) BRAF mutations were detected in patients <50 years. The inclusion of BRAF testing led to high risk of missing LS patients and increased costs at age <50 years. BRAF testing in patients <50 years carries a high risk of missing a hereditary cancer predisposition and is cost‐inefficient. We suggest direct referral of MSI CRC patients <50 years to genetic counseling without BRAF testing.
What's new?
Lynch syndrome (LS) is the most common hereditary colorectal cancer. While these cancers usually show microsatellite instability (MSI), most MSI tumors are sporadic. Here, the authors evaluated the usefulness of testing for BRAF mutations as a way to distinguish LS cancers from sporadic cases. They found that the frequency of tumors carrying BRAF mutations in LS patients under age 50 is very similar to the frequency of those mutations in MSI cancers from that age group, suggesting that there's substantial overlap between the two groups. Thus, BRAF mutation status should not be used to exclude LS in patients under 50.</description><subject>Age</subject><subject>Age Factors</subject><subject>Aged</subject><subject>Amino Acid Substitution</subject><subject>BRAF mutation testing</subject><subject>Cancer</subject><subject>Colorectal cancer</subject><subject>Colorectal carcinoma</subject><subject>Colorectal Neoplasms, Hereditary Nonpolyposis - diagnosis</subject><subject>Colorectal Neoplasms, Hereditary Nonpolyposis - genetics</subject><subject>Early Detection of Cancer - methods</subject><subject>Female</subject><subject>Genetic counseling</subject><subject>Genetic disorders</subject><subject>Genetic Markers</subject><subject>hereditary cancer syndrome</subject><subject>Humans</subject><subject>Lynch syndrome diagnostics</subject><subject>Male</subject><subject>Medical research</subject><subject>Microsatellite Instability</subject><subject>microsatellite instability colorectal cancer</subject><subject>Middle Aged</subject><subject>Mutation</subject><subject>Mutation Rate</subject><subject>Population studies</subject><subject>Proto-Oncogene Proteins B-raf - genetics</subject><subject>Sensitivity and Specificity</subject><issn>0020-7136</issn><issn>1097-0215</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>EIF</sourceid><recordid>eNp1kL1OwzAUhS0EoqUw8ALIEhNDWv_ETjKWikJRJaQKZsuNr0uqxglOIpSNR-AZeRJSUtiY7nA-fffoIHRJyZgSwibZNh1zziJ-hIaUJFFAGBXHaNhlJIgolwN0VlVbQigVJDxFA87iSAjBh2g13cDXx6eBEpwBV-MSvC18rl0KuLD4djWd47ypdZ0VDtdQ1Znb4MzhZevSV1y1zvgiB2wyvXFFl6bVOTqxelfBxeGO0Mv87nn2ECyf7hez6TJIeRzzAGxoOGOWydRqqs2-sxQiklxIBjKJuRSxAJ2GwLTlFoCtE5kYzbnWseB8hK57b-mLt6ZrprZF4133UrEwFExENKQdddNTqS-qyoNVpc9y7VtFidqvp7r11M96HXt1MDbrHMwf-TtXB0x64D3bQfu_SS0eZ73yG8v1eUc</recordid><startdate>20201115</startdate><enddate>20201115</enddate><creator>Bläker, Hendrik</creator><creator>Haupt, Saskia</creator><creator>Morak, Monika</creator><creator>Holinski‐Feder, Elke</creator><creator>Arnold, Alexander</creator><creator>Horst, David</creator><creator>Sieber‐Frank, Julia</creator><creator>Seidler, Florian</creator><creator>Winterfeld, Moritz</creator><creator>Alwers, Elizabeth</creator><creator>Chang‐Claude, Jenny</creator><creator>Brenner, Hermann</creator><creator>Roth, Wilfried</creator><creator>Engel, Christoph</creator><creator>Löffler, Markus</creator><creator>Möslein, Gabriela</creator><creator>Schackert, Hans‐Konrad</creator><creator>Weitz, Jürgen</creator><creator>Perne, Claudia</creator><creator>Aretz, Stefan</creator><creator>Hüneburg, Robert</creator><creator>Schmiegel, Wolff</creator><creator>Vangala, Deepak</creator><creator>Rahner, Nils</creator><creator>Steinke‐Lange, Verena</creator><creator>Heuveline, Vincent</creator><creator>von Knebel Doeberitz, Magnus</creator><creator>Ahadova, Aysel</creator><creator>Hoffmeister, Michael</creator><creator>Kloor, Matthias</creator><general>John Wiley & Sons, Inc</general><general>Wiley Subscription Services, Inc</general><scope>24P</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>7TO</scope><scope>7U9</scope><scope>H94</scope><scope>K9.</scope><orcidid>https://orcid.org/0000-0001-8491-3234</orcidid><orcidid>https://orcid.org/0000-0001-9890-0450</orcidid><orcidid>https://orcid.org/0000-0002-7247-282X</orcidid></search><sort><creationdate>20201115</creationdate><title>Age‐dependent performance of BRAF mutation testing in Lynch syndrome diagnostics</title><author>Bläker, Hendrik ; Haupt, Saskia ; Morak, Monika ; Holinski‐Feder, Elke ; Arnold, Alexander ; Horst, David ; Sieber‐Frank, Julia ; Seidler, Florian ; Winterfeld, Moritz ; Alwers, Elizabeth ; Chang‐Claude, Jenny ; Brenner, Hermann ; Roth, Wilfried ; Engel, Christoph ; Löffler, Markus ; Möslein, Gabriela ; Schackert, Hans‐Konrad ; Weitz, Jürgen ; Perne, Claudia ; Aretz, Stefan ; Hüneburg, Robert ; Schmiegel, Wolff ; Vangala, Deepak ; Rahner, Nils ; Steinke‐Lange, Verena ; Heuveline, Vincent ; von Knebel Doeberitz, Magnus ; Ahadova, Aysel ; Hoffmeister, Michael ; Kloor, Matthias</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3883-ef4d322f26cfa1ad0215655763562e69836585eac4e2af3fee2b969da33aa8533</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Age</topic><topic>Age Factors</topic><topic>Aged</topic><topic>Amino Acid Substitution</topic><topic>BRAF mutation testing</topic><topic>Cancer</topic><topic>Colorectal cancer</topic><topic>Colorectal carcinoma</topic><topic>Colorectal Neoplasms, Hereditary Nonpolyposis - diagnosis</topic><topic>Colorectal Neoplasms, Hereditary Nonpolyposis - genetics</topic><topic>Early Detection of Cancer - methods</topic><topic>Female</topic><topic>Genetic counseling</topic><topic>Genetic disorders</topic><topic>Genetic Markers</topic><topic>hereditary cancer syndrome</topic><topic>Humans</topic><topic>Lynch syndrome diagnostics</topic><topic>Male</topic><topic>Medical research</topic><topic>Microsatellite Instability</topic><topic>microsatellite instability colorectal cancer</topic><topic>Middle Aged</topic><topic>Mutation</topic><topic>Mutation Rate</topic><topic>Population studies</topic><topic>Proto-Oncogene Proteins B-raf - genetics</topic><topic>Sensitivity and Specificity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bläker, Hendrik</creatorcontrib><creatorcontrib>Haupt, Saskia</creatorcontrib><creatorcontrib>Morak, Monika</creatorcontrib><creatorcontrib>Holinski‐Feder, Elke</creatorcontrib><creatorcontrib>Arnold, Alexander</creatorcontrib><creatorcontrib>Horst, David</creatorcontrib><creatorcontrib>Sieber‐Frank, Julia</creatorcontrib><creatorcontrib>Seidler, Florian</creatorcontrib><creatorcontrib>Winterfeld, Moritz</creatorcontrib><creatorcontrib>Alwers, Elizabeth</creatorcontrib><creatorcontrib>Chang‐Claude, Jenny</creatorcontrib><creatorcontrib>Brenner, Hermann</creatorcontrib><creatorcontrib>Roth, Wilfried</creatorcontrib><creatorcontrib>Engel, Christoph</creatorcontrib><creatorcontrib>Löffler, Markus</creatorcontrib><creatorcontrib>Möslein, Gabriela</creatorcontrib><creatorcontrib>Schackert, Hans‐Konrad</creatorcontrib><creatorcontrib>Weitz, Jürgen</creatorcontrib><creatorcontrib>Perne, Claudia</creatorcontrib><creatorcontrib>Aretz, Stefan</creatorcontrib><creatorcontrib>Hüneburg, Robert</creatorcontrib><creatorcontrib>Schmiegel, Wolff</creatorcontrib><creatorcontrib>Vangala, Deepak</creatorcontrib><creatorcontrib>Rahner, Nils</creatorcontrib><creatorcontrib>Steinke‐Lange, Verena</creatorcontrib><creatorcontrib>Heuveline, Vincent</creatorcontrib><creatorcontrib>von Knebel Doeberitz, Magnus</creatorcontrib><creatorcontrib>Ahadova, Aysel</creatorcontrib><creatorcontrib>Hoffmeister, Michael</creatorcontrib><creatorcontrib>Kloor, Matthias</creatorcontrib><creatorcontrib>German Consortium for Familial Intestinal Cancer</creatorcontrib><creatorcontrib>The German Consortium for Familial Intestinal Cancer</creatorcontrib><collection>Wiley Online Library Open Access</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>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><jtitle>International journal of cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bläker, Hendrik</au><au>Haupt, Saskia</au><au>Morak, Monika</au><au>Holinski‐Feder, Elke</au><au>Arnold, Alexander</au><au>Horst, David</au><au>Sieber‐Frank, Julia</au><au>Seidler, Florian</au><au>Winterfeld, Moritz</au><au>Alwers, Elizabeth</au><au>Chang‐Claude, Jenny</au><au>Brenner, Hermann</au><au>Roth, Wilfried</au><au>Engel, Christoph</au><au>Löffler, Markus</au><au>Möslein, Gabriela</au><au>Schackert, Hans‐Konrad</au><au>Weitz, Jürgen</au><au>Perne, Claudia</au><au>Aretz, Stefan</au><au>Hüneburg, Robert</au><au>Schmiegel, Wolff</au><au>Vangala, Deepak</au><au>Rahner, Nils</au><au>Steinke‐Lange, Verena</au><au>Heuveline, Vincent</au><au>von Knebel Doeberitz, Magnus</au><au>Ahadova, Aysel</au><au>Hoffmeister, Michael</au><au>Kloor, Matthias</au><aucorp>German Consortium for Familial Intestinal Cancer</aucorp><aucorp>The German Consortium for Familial Intestinal Cancer</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Age‐dependent performance of BRAF mutation testing in Lynch syndrome diagnostics</atitle><jtitle>International journal of cancer</jtitle><addtitle>Int J Cancer</addtitle><date>2020-11-15</date><risdate>2020</risdate><volume>147</volume><issue>10</issue><spage>2801</spage><epage>2810</epage><pages>2801-2810</pages><issn>0020-7136</issn><eissn>1097-0215</eissn><abstract>BRAF V600E mutations have been reported as a marker of sporadic microsatellite instability (MSI) colorectal cancer (CRC). Current international diagnostic guidelines recommend BRAF mutation testing in MSI CRC patients to predict low risk of Lynch syndrome (LS). We evaluated the age‐specific performance of BRAF testing in LS diagnostics. We systematically compared the prevalence of BRAF mutations in LS‐associated CRCs and unselected MSI CRCs in different age groups as available from published studies, databases and population‐based patient cohorts. Sensitivity/specificity analysis of BRAF testing for exclusion of LS and cost calculations were performed. Among 969 MSI CRCs from LS carriers in the literature and German HNPCC Consortium, 15 (1.6%) harbored BRAF mutations. Six of seven LS patients with BRAF‐mutant CRC and reported age were <50 years. Among 339 of 756 (44.8%) of BRAF mutations detected in unselected MSI CRC, only 2 of 339 (0.6%) BRAF mutations were detected in patients <50 years. The inclusion of BRAF testing led to high risk of missing LS patients and increased costs at age <50 years. BRAF testing in patients <50 years carries a high risk of missing a hereditary cancer predisposition and is cost‐inefficient. We suggest direct referral of MSI CRC patients <50 years to genetic counseling without BRAF testing.
What's new?
Lynch syndrome (LS) is the most common hereditary colorectal cancer. While these cancers usually show microsatellite instability (MSI), most MSI tumors are sporadic. Here, the authors evaluated the usefulness of testing for BRAF mutations as a way to distinguish LS cancers from sporadic cases. They found that the frequency of tumors carrying BRAF mutations in LS patients under age 50 is very similar to the frequency of those mutations in MSI cancers from that age group, suggesting that there's substantial overlap between the two groups. Thus, BRAF mutation status should not be used to exclude LS in patients under 50.</abstract><cop>Hoboken, USA</cop><pub>John Wiley & Sons, Inc</pub><pmid>32875553</pmid><doi>10.1002/ijc.33273</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0001-8491-3234</orcidid><orcidid>https://orcid.org/0000-0001-9890-0450</orcidid><orcidid>https://orcid.org/0000-0002-7247-282X</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0020-7136 |
| ispartof | International journal of cancer, 2020-11, Vol.147 (10), p.2801-2810 |
| issn | 0020-7136 1097-0215 |
| language | eng |
| recordid | cdi_proquest_journals_2445257141 |
| source | MEDLINE; Wiley Online Library Journals Frontfile Complete; EZB-FREE-00999 freely available EZB journals |
| subjects | Age Age Factors Aged Amino Acid Substitution BRAF mutation testing Cancer Colorectal cancer Colorectal carcinoma Colorectal Neoplasms, Hereditary Nonpolyposis - diagnosis Colorectal Neoplasms, Hereditary Nonpolyposis - genetics Early Detection of Cancer - methods Female Genetic counseling Genetic disorders Genetic Markers hereditary cancer syndrome Humans Lynch syndrome diagnostics Male Medical research Microsatellite Instability microsatellite instability colorectal cancer Middle Aged Mutation Mutation Rate Population studies Proto-Oncogene Proteins B-raf - genetics Sensitivity and Specificity |
| title | Age‐dependent performance of BRAF mutation testing in Lynch syndrome diagnostics |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-08T12%3A15%3A37IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Age%E2%80%90dependent%20performance%20of%20BRAF%20mutation%20testing%20in%20Lynch%20syndrome%20diagnostics&rft.jtitle=International%20journal%20of%20cancer&rft.au=Bl%C3%A4ker,%20Hendrik&rft.aucorp=German%20Consortium%20for%20Familial%20Intestinal%20Cancer&rft.date=2020-11-15&rft.volume=147&rft.issue=10&rft.spage=2801&rft.epage=2810&rft.pages=2801-2810&rft.issn=0020-7136&rft.eissn=1097-0215&rft_id=info:doi/10.1002/ijc.33273&rft_dat=%3Cproquest_cross%3E2445257141%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2445257141&rft_id=info:pmid/32875553&rfr_iscdi=true |