A mosaic PIK3CA variant in a young adult with diffuse gastric cancer: case report
Hereditary diffuse gastric cancer (HDGC) is associated with germline deleterious variants in CDH1 and CTNNA1. The majority of HDGC-suspected patients are still genetically unresolved, raising the need for identification of novel HDGC predisposing genes. Under the collaborative environment of the SOL...
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| Veröffentlicht in: | European journal of human genetics : EJHG 2021-09, Vol.29 (9), p.1354-1358 |
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| creator | Te Paske, Iris B A W Garcia-Pelaez, José Sommer, Anna K Matalonga, Leslie Starzynska, Teresa Jakubowska, Anna van der Post, Rachel S Lubinski, Jan Oliveira, Carla Hoogerbrugge, Nicoline de Voer, Richarda M |
| description | Hereditary diffuse gastric cancer (HDGC) is associated with germline deleterious variants in CDH1 and CTNNA1. The majority of HDGC-suspected patients are still genetically unresolved, raising the need for identification of novel HDGC predisposing genes. Under the collaborative environment of the SOLVE-RD consortium, re-analysis of whole-exome sequencing data from unresolved gastric cancer cases (n = 83) identified a mosaic missense variant in PIK3CA in a 25-year-old female with diffuse gastric cancer (DGC) without familial history for cancer. The variant, c.3140A>G p.(His1047Arg), a known cancer-related somatic hotspot, was present at a low variant allele frequency (18%) in leukocyte-derived DNA. Somatic variants in PIK3CA are usually associated with overgrowth, a phenotype that was not observed in this patient. This report highlights mosaicism as a potential, and understudied, mechanism in the etiology of DGC. |
| doi_str_mv | 10.1038/s41431-021-00853-6 |
| format | Article |
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The majority of HDGC-suspected patients are still genetically unresolved, raising the need for identification of novel HDGC predisposing genes. Under the collaborative environment of the SOLVE-RD consortium, re-analysis of whole-exome sequencing data from unresolved gastric cancer cases (n = 83) identified a mosaic missense variant in PIK3CA in a 25-year-old female with diffuse gastric cancer (DGC) without familial history for cancer. The variant, c.3140A>G p.(His1047Arg), a known cancer-related somatic hotspot, was present at a low variant allele frequency (18%) in leukocyte-derived DNA. Somatic variants in PIK3CA are usually associated with overgrowth, a phenotype that was not observed in this patient. This report highlights mosaicism as a potential, and understudied, mechanism in the etiology of DGC.</description><identifier>ISSN: 1018-4813</identifier><identifier>EISSN: 1476-5438</identifier><identifier>DOI: 10.1038/s41431-021-00853-6</identifier><identifier>PMID: 34075207</identifier><language>eng</language><publisher>England: Nature Publishing Group</publisher><subject>Adult ; Brief Communication ; Case reports ; Class I Phosphatidylinositol 3-Kinases - genetics ; E-cadherin ; Etiology ; Female ; Gastric cancer ; Gene frequency ; Humans ; Mosaicism ; Mutation, Missense ; Phenotypes ; Stomach Neoplasms - genetics ; Stomach Neoplasms - pathology ; Whole Exome Sequencing</subject><ispartof>European journal of human genetics : EJHG, 2021-09, Vol.29 (9), p.1354-1358</ispartof><rights>2021. The Author(s).</rights><rights>The Author(s) 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). 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This report highlights mosaicism as a potential, and understudied, mechanism in the etiology of DGC.</description><subject>Adult</subject><subject>Brief Communication</subject><subject>Case reports</subject><subject>Class I Phosphatidylinositol 3-Kinases - genetics</subject><subject>E-cadherin</subject><subject>Etiology</subject><subject>Female</subject><subject>Gastric cancer</subject><subject>Gene frequency</subject><subject>Humans</subject><subject>Mosaicism</subject><subject>Mutation, Missense</subject><subject>Phenotypes</subject><subject>Stomach Neoplasms - genetics</subject><subject>Stomach Neoplasms - pathology</subject><subject>Whole Exome Sequencing</subject><issn>1018-4813</issn><issn>1476-5438</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNpdkV9LHTEQxUOp1D_1C_ShBPriy-okk02yPhQuF6uiYIX6HHKz2Wtk7-Y22VX89k29KurDMEPmdw4ZDiHfGBwyQH2UBRPIKuClQNdYyU9khwklq1qg_lxmYLoSmuE22c35DqAsFftCtlGAqjmoHXI9o6uYbXD09_kFzmf03qZgh5GGgVr6GKdhSW079SN9COMtbUPXTdnTpc1jKiJnB-fTcenlMfl1TONXstXZPvv9575Hbn6d_JmfVZdXp-fz2WXlBMJYcWwca5RgWoETHToQslWt0FbrBVsoxAaAS7bg0HXMNyAb7lzTNq71vG447pGfG9_1tFj51vlhTLY36xRWNj2aaIN5vxnCrVnGe6OFAKmgGBw8G6T4d_J5NKuQne97O_g4ZcNrlEIiA13QHx_QuziloZxXKMWxLpasUHxDuRRzTr57_QwD8z8xs0nMlMTMU2JGFtH3t2e8Sl4iwn8H8I9w</recordid><startdate>20210901</startdate><enddate>20210901</enddate><creator>Te Paske, Iris B A W</creator><creator>Garcia-Pelaez, José</creator><creator>Sommer, Anna K</creator><creator>Matalonga, Leslie</creator><creator>Starzynska, Teresa</creator><creator>Jakubowska, Anna</creator><creator>van der Post, Rachel S</creator><creator>Lubinski, Jan</creator><creator>Oliveira, Carla</creator><creator>Hoogerbrugge, Nicoline</creator><creator>de Voer, Richarda M</creator><general>Nature Publishing Group</general><general>Springer International Publishing</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>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-5573-2397</orcidid><orcidid>https://orcid.org/0000-0002-8222-0343</orcidid><orcidid>https://orcid.org/0000-0003-2393-8141</orcidid><orcidid>https://orcid.org/0000-0001-6850-9290</orcidid><orcidid>https://orcid.org/0000-0002-5650-0501</orcidid></search><sort><creationdate>20210901</creationdate><title>A mosaic PIK3CA variant in a young adult with diffuse gastric cancer: case report</title><author>Te Paske, Iris B A W ; Garcia-Pelaez, José ; Sommer, Anna K ; Matalonga, Leslie ; Starzynska, Teresa ; Jakubowska, Anna ; van der Post, Rachel S ; Lubinski, Jan ; Oliveira, Carla ; Hoogerbrugge, Nicoline ; de Voer, Richarda M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c430t-239c19741870c4f3c046d7d48a88b1b733900261b20ff1e90692cc9d9cde25923</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Adult</topic><topic>Brief Communication</topic><topic>Case reports</topic><topic>Class I Phosphatidylinositol 3-Kinases - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>European journal of human genetics : EJHG</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Te Paske, Iris B A W</au><au>Garcia-Pelaez, José</au><au>Sommer, Anna K</au><au>Matalonga, Leslie</au><au>Starzynska, Teresa</au><au>Jakubowska, Anna</au><au>van der Post, Rachel S</au><au>Lubinski, Jan</au><au>Oliveira, Carla</au><au>Hoogerbrugge, Nicoline</au><au>de Voer, Richarda M</au><aucorp>Solve-RD-GENTURIS group</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A mosaic PIK3CA variant in a young adult with diffuse gastric cancer: case report</atitle><jtitle>European journal of human genetics : EJHG</jtitle><addtitle>Eur J Hum Genet</addtitle><date>2021-09-01</date><risdate>2021</risdate><volume>29</volume><issue>9</issue><spage>1354</spage><epage>1358</epage><pages>1354-1358</pages><issn>1018-4813</issn><eissn>1476-5438</eissn><abstract>Hereditary diffuse gastric cancer (HDGC) is associated with germline deleterious variants in CDH1 and CTNNA1. 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| source | MEDLINE; Springer Nature - Complete Springer Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | Adult Brief Communication Case reports Class I Phosphatidylinositol 3-Kinases - genetics E-cadherin Etiology Female Gastric cancer Gene frequency Humans Mosaicism Mutation, Missense Phenotypes Stomach Neoplasms - genetics Stomach Neoplasms - pathology Whole Exome Sequencing |
| title | A mosaic PIK3CA variant in a young adult with diffuse gastric cancer: case report |
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