A frame-shift mutation of PMS2 is a widespread cause of Lynch syndrome
Identifieur interne : 000782 ( Pmc/Curation ); précédent : 000781; suivant : 000783A frame-shift mutation of PMS2 is a widespread cause of Lynch syndrome
Auteurs : M. Clendenning [États-Unis] ; L. Senter [États-Unis] ; H. Hampel [États-Unis] ; K Lagerstedt Robinson [Suède] ; S. Sun [États-Unis] ; D. Buchanan [Australie] ; M D Walsh [Australie] ; M. Nilbert [Suède] ; J. Green [Canada] ; J. Potter [États-Unis] ; A. Lindblom [Suède] ; A. De La Chapelle [États-Unis]Source :
- Journal of medical genetics [ 0022-2593 ] ; 2008.
Abstract
When compared to the other mismatch repair genes involved in Lynch syndrome, the identification of mutations within
Using a recently developed method for detecting
We have identified a frequently occurring frame-shift mutation (c.736_741del6ins11) in 12 ostensibly unrelated Lynch syndrome patients (20% of patients we have identified with a deleterious mutation in
Ancestral analysis indicates that this mutation is enriched in individuals with British and Swedish ancestry. We estimate that there are >10 000 carriers of this mutation in the USA alone. The identification of both the mutation and the common haplotype in one Swedish control sample (n = 225), along with evidence that Lynch syndrome associated cancers are rarer than expected in the probands’ families, would suggest that this is a prevalent mutation with reduced penetrance.
Url:
DOI: 10.1136/jmg.2007.056150
PubMed: 18178629
PubMed Central: 4339871
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Senter</name><affiliation wicri:level="1"><nlm:aff id="A1">Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio</wicri:regionArea></affiliation></author><author><name sortKey="Hampel, H" sort="Hampel, H" uniqKey="Hampel H" first="H" last="Hampel">H. 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Sun</name><affiliation wicri:level="1"><nlm:aff id="A3">Mathematical Biosciences Institute, The Ohio State University, Columbus, Ohio, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Mathematical Biosciences Institute, The Ohio State University, Columbus, Ohio</wicri:regionArea></affiliation></author><author><name sortKey="Buchanan, D" sort="Buchanan, D" uniqKey="Buchanan D" first="D" last="Buchanan">D. Buchanan</name><affiliation wicri:level="1"><nlm:aff id="A4">Familial Cancer Laboratory, Queensland Institute of Medical Research, Herston, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Familial Cancer Laboratory, Queensland Institute of Medical Research, Herston</wicri:regionArea></affiliation></author><author><name sortKey="Walsh, M D" sort="Walsh, M D" uniqKey="Walsh M" first="M D" last="Walsh">M D Walsh</name><affiliation wicri:level="1"><nlm:aff id="A4">Familial Cancer Laboratory, Queensland Institute of Medical Research, Herston, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Familial Cancer Laboratory, Queensland Institute of Medical Research, Herston</wicri:regionArea></affiliation></author><author><name sortKey="Nilbert, M" sort="Nilbert, M" uniqKey="Nilbert M" first="M" last="Nilbert">M. Nilbert</name><affiliation wicri:level="1"><nlm:aff id="A5">Department of Oncology, Clinical Sciences, Lund University, Lund, Sweden</nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Oncology, Clinical Sciences, Lund University, Lund</wicri:regionArea></affiliation></author><author><name sortKey="Green, J" sort="Green, J" uniqKey="Green J" first="J" last="Green">J. Green</name><affiliation wicri:level="1"><nlm:aff id="A6">Discipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, St John’s, Newfoundland, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Discipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, St John’s, Newfoundland</wicri:regionArea></affiliation></author><author><name sortKey="Potter, J" sort="Potter, J" uniqKey="Potter J" first="J" last="Potter">J. Potter</name><affiliation wicri:level="1"><nlm:aff id="A7">Fred Hutchinson Cancer Research Center, Seattle, Washington, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Fred Hutchinson Cancer Research Center, Seattle, Washington</wicri:regionArea></affiliation></author><author><name sortKey="Lindblom, A" sort="Lindblom, A" uniqKey="Lindblom A" first="A" last="Lindblom">A. Lindblom</name><affiliation wicri:level="1"><nlm:aff id="A2">Karolinska Institute, Department of Molecular Medicine, Stockholm, Sweden</nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea>Karolinska Institute, Department of Molecular Medicine, Stockholm</wicri:regionArea></affiliation></author><author><name sortKey="De La Chapelle, A" sort="De La Chapelle, A" uniqKey="De La Chapelle A" first="A" last="De La Chapelle">A. De La Chapelle</name><affiliation wicri:level="1"><nlm:aff id="A1">Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">18178629</idno><idno type="pmc">4339871</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4339871</idno><idno type="RBID">PMC:4339871</idno><idno type="doi">10.1136/jmg.2007.056150</idno><date when="2008">2008</date><idno type="wicri:Area/Pmc/Corpus">000782</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000782</idno><idno type="wicri:Area/Pmc/Curation">000782</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000782</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">A frame-shift mutation of <italic>PMS2</italic> is a widespread cause of Lynch syndrome</title><author><name sortKey="Clendenning, M" sort="Clendenning, M" uniqKey="Clendenning M" first="M" last="Clendenning">M. Clendenning</name><affiliation wicri:level="1"><nlm:aff id="A1">Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio</wicri:regionArea></affiliation></author><author><name sortKey="Senter, L" sort="Senter, L" uniqKey="Senter L" first="L" last="Senter">L. Senter</name><affiliation wicri:level="1"><nlm:aff id="A1">Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio</wicri:regionArea></affiliation></author><author><name sortKey="Hampel, H" sort="Hampel, H" uniqKey="Hampel H" first="H" last="Hampel">H. Hampel</name><affiliation wicri:level="1"><nlm:aff id="A1">Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio</wicri:regionArea></affiliation></author><author><name sortKey="Robinson, K Lagerstedt" sort="Robinson, K Lagerstedt" uniqKey="Robinson K" first="K Lagerstedt" last="Robinson">K Lagerstedt Robinson</name><affiliation wicri:level="1"><nlm:aff id="A2">Karolinska Institute, Department of Molecular Medicine, Stockholm, Sweden</nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea>Karolinska Institute, Department of Molecular Medicine, Stockholm</wicri:regionArea></affiliation></author><author><name sortKey="Sun, S" sort="Sun, S" uniqKey="Sun S" first="S" last="Sun">S. Sun</name><affiliation wicri:level="1"><nlm:aff id="A3">Mathematical Biosciences Institute, The Ohio State University, Columbus, Ohio, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Mathematical Biosciences Institute, The Ohio State University, Columbus, Ohio</wicri:regionArea></affiliation></author><author><name sortKey="Buchanan, D" sort="Buchanan, D" uniqKey="Buchanan D" first="D" last="Buchanan">D. Buchanan</name><affiliation wicri:level="1"><nlm:aff id="A4">Familial Cancer Laboratory, Queensland Institute of Medical Research, Herston, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Familial Cancer Laboratory, Queensland Institute of Medical Research, Herston</wicri:regionArea></affiliation></author><author><name sortKey="Walsh, M D" sort="Walsh, M D" uniqKey="Walsh M" first="M D" last="Walsh">M D Walsh</name><affiliation wicri:level="1"><nlm:aff id="A4">Familial Cancer Laboratory, Queensland Institute of Medical Research, Herston, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Familial Cancer Laboratory, Queensland Institute of Medical Research, Herston</wicri:regionArea></affiliation></author><author><name sortKey="Nilbert, M" sort="Nilbert, M" uniqKey="Nilbert M" first="M" last="Nilbert">M. Nilbert</name><affiliation wicri:level="1"><nlm:aff id="A5">Department of Oncology, Clinical Sciences, Lund University, Lund, Sweden</nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Oncology, Clinical Sciences, Lund University, Lund</wicri:regionArea></affiliation></author><author><name sortKey="Green, J" sort="Green, J" uniqKey="Green J" first="J" last="Green">J. Green</name><affiliation wicri:level="1"><nlm:aff id="A6">Discipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, St John’s, Newfoundland, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Discipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, St John’s, Newfoundland</wicri:regionArea></affiliation></author><author><name sortKey="Potter, J" sort="Potter, J" uniqKey="Potter J" first="J" last="Potter">J. Potter</name><affiliation wicri:level="1"><nlm:aff id="A7">Fred Hutchinson Cancer Research Center, Seattle, Washington, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Fred Hutchinson Cancer Research Center, Seattle, Washington</wicri:regionArea></affiliation></author><author><name sortKey="Lindblom, A" sort="Lindblom, A" uniqKey="Lindblom A" first="A" last="Lindblom">A. Lindblom</name><affiliation wicri:level="1"><nlm:aff id="A2">Karolinska Institute, Department of Molecular Medicine, Stockholm, Sweden</nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea>Karolinska Institute, Department of Molecular Medicine, Stockholm</wicri:regionArea></affiliation></author><author><name sortKey="De La Chapelle, A" sort="De La Chapelle, A" uniqKey="De La Chapelle A" first="A" last="De La Chapelle">A. De La Chapelle</name><affiliation wicri:level="1"><nlm:aff id="A1">Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio</wicri:regionArea></affiliation></author></analytic><series><title level="j">Journal of medical genetics</title><idno type="ISSN">0022-2593</idno><idno type="eISSN">1468-6244</idno><imprint><date when="2008">2008</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec id="S1"><title>Background</title><p id="P1">When compared to the other mismatch repair genes involved in Lynch syndrome, the identification of mutations within <italic>PMS2</italic> has been limited (<2% of all identified mutations), yet the immunohistochemical analysis of tumour samples indicates that approximately 5% of Lynch syndrome cases are caused by PMS2. This disparity is primarily due to complications in the study of this gene caused by interference from pseudogene sequences.</p></sec><sec id="S2"><title>Methods</title><p id="P2">Using a recently developed method for detecting <italic>PMS2</italic> specific mutations, we have screened 99 patients who are likely candidates for <italic>PMS2</italic> mutations based on immunohistochemical analysis.</p></sec><sec id="S3"><title>Results</title><p id="P3">We have identified a frequently occurring frame-shift mutation (c.736_741del6ins11) in 12 ostensibly unrelated Lynch syndrome patients (20% of patients we have identified with a deleterious mutation in <italic>PMS2</italic>, n = 61). These individuals all display the rare allele (population frequency <0.05) at a single nucleotide polymorphism (SNP) in exon 11, and have been shown to possess a short common haplotype, allowing us to calculate that the mutation arose around 1625 years ago (65 generations; 95% confidence interval 22 to 120).</p></sec><sec id="S4"><title>Conclusion</title><p id="P4">Ancestral analysis indicates that this mutation is enriched in individuals with British and Swedish ancestry. We estimate that there are >10 000 carriers of this mutation in the USA alone. The identification of both the mutation and the common haplotype in one Swedish control sample (n = 225), along with evidence that Lynch syndrome associated cancers are rarer than expected in the probands’ families, would suggest that this is a prevalent mutation with reduced penetrance.</p></sec></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">2985087R</journal-id><journal-id journal-id-type="pubmed-jr-id">4945</journal-id><journal-id journal-id-type="nlm-ta">J Med Genet</journal-id><journal-id journal-id-type="iso-abbrev">J. Med. Genet.</journal-id><journal-title-group><journal-title>Journal of medical genetics</journal-title></journal-title-group><issn pub-type="ppub">0022-2593</issn><issn pub-type="epub">1468-6244</issn></journal-meta><article-meta><article-id pub-id-type="pmid">18178629</article-id><article-id pub-id-type="pmc">4339871</article-id><article-id pub-id-type="doi">10.1136/jmg.2007.056150</article-id><article-id pub-id-type="manuscript">NIHMS665590</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>A frame-shift mutation of <italic>PMS2</italic> is a widespread cause of Lynch syndrome</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Clendenning</surname><given-names>M</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Senter</surname><given-names>L</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Hampel</surname><given-names>H</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Robinson</surname><given-names>K Lagerstedt</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Sun</surname><given-names>S</given-names></name><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><name><surname>Buchanan</surname><given-names>D</given-names></name><xref ref-type="aff" rid="A4">4</xref></contrib><contrib contrib-type="author"><name><surname>Walsh</surname><given-names>M D</given-names></name><xref ref-type="aff" rid="A4">4</xref></contrib><contrib contrib-type="author"><name><surname>Nilbert</surname><given-names>M</given-names></name><xref ref-type="aff" rid="A5">5</xref></contrib><contrib contrib-type="author"><name><surname>Green</surname><given-names>J</given-names></name><xref ref-type="aff" rid="A6">6</xref></contrib><contrib contrib-type="author"><name><surname>Potter</surname><given-names>J</given-names></name><xref ref-type="aff" rid="A7">7</xref></contrib><contrib contrib-type="author"><name><surname>Lindblom</surname><given-names>A</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>de la Chapelle</surname><given-names>A</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib></contrib-group><aff id="A1"><label>1</label>Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA</aff><aff id="A2"><label>2</label>Karolinska Institute, Department of Molecular Medicine, Stockholm, Sweden</aff><aff id="A3"><label>3</label>Mathematical Biosciences Institute, The Ohio State University, Columbus, Ohio, USA</aff><aff id="A4"><label>4</label>Familial Cancer Laboratory, Queensland Institute of Medical Research, Herston, Australia</aff><aff id="A5"><label>5</label>Department of Oncology, Clinical Sciences, Lund University, Lund, Sweden</aff><aff id="A6"><label>6</label>Discipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, St John’s, Newfoundland, Canada</aff><aff id="A7"><label>7</label>Fred Hutchinson Cancer Research Center, Seattle, Washington, USA</aff><author-notes><corresp id="FN1">Correspondence to: Professor A de la Chapelle, Human Cancer Genetics, Room 804, Biomedical Research Tower, 460 West 12th Avenue, Columbus, OH 43210, USA; <email>albert.delachapelle@osumc.edu</email></corresp></author-notes><pub-date pub-type="nihms-submitted"><day>20</day><month>2</month><year>2015</year></pub-date><pub-date pub-type="epub"><day>04</day><month>1</month><year>2008</year></pub-date><pub-date pub-type="ppub"><month>6</month><year>2008</year></pub-date><pub-date pub-type="pmc-release"><day>25</day><month>2</month><year>2015</year></pub-date><volume>45</volume><issue>6</issue><fpage>340</fpage><lpage>345</lpage><pmc-comment>elocation-id from pubmed: 10.1136/jmg.2007.056150</pmc-comment>
<abstract><sec id="S1"><title>Background</title><p id="P1">When compared to the other mismatch repair genes involved in Lynch syndrome, the identification of mutations within <italic>PMS2</italic> has been limited (<2% of all identified mutations), yet the immunohistochemical analysis of tumour samples indicates that approximately 5% of Lynch syndrome cases are caused by PMS2. This disparity is primarily due to complications in the study of this gene caused by interference from pseudogene sequences.</p></sec><sec id="S2"><title>Methods</title><p id="P2">Using a recently developed method for detecting <italic>PMS2</italic> specific mutations, we have screened 99 patients who are likely candidates for <italic>PMS2</italic> mutations based on immunohistochemical analysis.</p></sec><sec id="S3"><title>Results</title><p id="P3">We have identified a frequently occurring frame-shift mutation (c.736_741del6ins11) in 12 ostensibly unrelated Lynch syndrome patients (20% of patients we have identified with a deleterious mutation in <italic>PMS2</italic>, n = 61). These individuals all display the rare allele (population frequency <0.05) at a single nucleotide polymorphism (SNP) in exon 11, and have been shown to possess a short common haplotype, allowing us to calculate that the mutation arose around 1625 years ago (65 generations; 95% confidence interval 22 to 120).</p></sec><sec id="S4"><title>Conclusion</title><p id="P4">Ancestral analysis indicates that this mutation is enriched in individuals with British and Swedish ancestry. We estimate that there are >10 000 carriers of this mutation in the USA alone. The identification of both the mutation and the common haplotype in one Swedish control sample (n = 225), along with evidence that Lynch syndrome associated cancers are rarer than expected in the probands’ families, would suggest that this is a prevalent mutation with reduced penetrance.</p></sec></abstract></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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