{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T00:57:35Z","timestamp":1760317055934,"version":"build-2065373602"},"reference-count":48,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2021,3,25]],"date-time":"2021-03-25T00:00:00Z","timestamp":1616630400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2021,6,15]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Waldenstr\u00f6m macroglobulinemia (WM) is a rare chronic B\u2010cell lymphoma. Familial clustering of WM has been observed over the years. However, little is known about the contribution of inherited genetic variants to familial WM cases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The authors performed whole exome sequencing (WES) of germline DNA samples from twins, one diagnosed with WM and the other diagnosed with immunoglobulin M monoclonal gammopathy of undetermined significance, and their healthy siblings. Bioinformatics analysis of public biological databases was used to identify the most relevant familial WM candidate from WES. Transcript expression and protein levels of the familial WM candidate were evaluated in the WM patient and 2 unaffected members of the kindred.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among the 10 shared candidate mutations in the twins, the authors identified a novel heterozygous germline mutation in four and a half LIM domains protein 2 (<jats:italic>FHL2<\/jats:italic>; c.G226A, p.V76M) as a familial WM\u2013associated mutation. <jats:italic>FHL2<\/jats:italic> appeared to be connected with reported signaling pathways and disease\u2010driving genes such as <jats:italic>IL6<\/jats:italic> and <jats:italic>HCK<\/jats:italic> in WM. In addition, the authors found reduced <jats:italic>FHL2<\/jats:italic> messenger RNA and protein expression in peripheral blood samples from the patient with WM in comparison with the healthy siblings.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Taken together, these findings indicate that an <jats:italic>FHL2<\/jats:italic><jats:sup>g226a<\/jats:sup> mutation may play an important role in familial WM, and they provide new screening possibilities for familial cases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Lay Summary<\/jats:title><jats:p>\n<jats:list list-type=\"bullet\">\n\n<jats:list-item><jats:p>Familial clustering in Waldenstr\u00f6m macroglobulinemia (WM) has been observed over the years.<\/jats:p><\/jats:list-item>\n\n<jats:list-item><jats:p>The authors performed whole exome sequencing of germline DNA samples from twins, one diagnosed with WM and the other diagnosed with immunoglobulin M monoclonal gammopathy of undetermined significance, and their healthy siblings.<\/jats:p><\/jats:list-item>\n\n<jats:list-item><jats:p>Among the 10 shared candidate mutations in the twins, a novel heterozygous germline mutation in four and a half LIM domains protein 2 (<jats:italic>FHL2<\/jats:italic>; c.G226A, p.V76M) was identified as the most relevant familial WM candidate through bioinformatics analysis of a public database.<\/jats:p><\/jats:list-item>\n\n<jats:list-item><jats:p>Also, messenger RNA and protein expression of <jats:italic>FHL2<\/jats:italic> was significantly lower in peripheral blood mononuclear cells of the WM patient in comparison with the healthy siblings, and this suggested that the function of FHL2 was impaired when mutated.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.33454","type":"journal-article","created":{"date-parts":[[2021,3,25]],"date-time":"2021-03-25T10:28:29Z","timestamp":1616668109000},"page":"2039-2048","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Screening and identification of a novel FHL2 mutation by whole exome sequencing in twins with familial Waldenstr\u00f6m macroglobulinemia"],"prefix":"10.1002","volume":"127","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1199-5755","authenticated-orcid":false,"given":"Yike","family":"Wan","sequence":"first","affiliation":[{"name":"Department of Hematology Renji Hospital, School of Medicine, Shanghai Jiao Tong University Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuexin","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Hematology The First People's 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