{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T15:41:01Z","timestamp":1788536461640,"version":"build-2803163510"},"reference-count":40,"publisher":"National Academy of Sciences","issue":"35","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2009,9]]},"abstract":"<jats:p>\n                    Classical Hodgkin lymphoma (cHL) is a malignancy of B-cell origin in which the neoplastic cells, known as \u201cReed-Sternberg\u201d (RS) cells, are characteristically binucleated. Here we describe a family where multiple individuals developing cHL have inherited a reciprocal translocation between chromosomes 2 and 3. The translocation disrupts\n                    <jats:italic>KLHDC8B<\/jats:italic>\n                    , an uncharacterized gene from a region (3p21.31) previously implicated in lymphoma and related malignancies, resulting in its loss of expression. We tested\n                    <jats:italic>KLHDC8B<\/jats:italic>\n                    as a candidate gene for cHL and found that a 5\u2032-UTR polymorphism responsible for decreasing its translational expression is associated with cHL in probands from other families with cHL and segregates with disease in those pedigrees. In one of three informative sporadic cases of cHL, we detected loss of heterozygosity (LOH) for\n                    <jats:italic>KLHDC8B<\/jats:italic>\n                    in RS cells, but not reactive T lymphocytes, purified from a malignant lymph node.\n                    <jats:italic>KLHDC8B<\/jats:italic>\n                    encodes a protein predicted to contain seven kelch repeat domains. KLHDC8B is expressed during mitosis, where it localizes to the midbody structure connecting cells about to separate during cytokinesis, and it is degraded after cell division. Depletion of KLHDC8B through RNA interference leads to an increase in binucleated cells, implicating its reduced expression in the formation of cHL's signature RS cell.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0904231106","type":"journal-article","created":{"date-parts":[[2009,8,12]],"date-time":"2009-08-12T22:05:21Z","timestamp":1250114721000},"page":"14920-14925","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":58,"title":["Mutations in a gene encoding a midbody kelch protein in familial and sporadic classical Hodgkin lymphoma lead to binucleated cells"],"prefix":"10.1073","volume":"106","author":[{"given":"Stephen J.","family":"Salipante","sequence":"first","affiliation":[{"name":"Department of Genome Sciences,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew E.","family":"Mealiffe","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy","family":"Wechsler","sequence":"additional","affiliation":[{"name":"Department of Pathology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maxwell M.","family":"Krem","sequence":"additional","affiliation":[{"name":"Medical Oncology Program,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yajuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinae","family":"Namkoong","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Govind","family":"Bhagat","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Physicians and Surgeons of Columbia University, New York, NY 10032;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomas","family":"Kirchhoff","sequence":"additional","affiliation":[{"name":"Memorial Sloan-Kettering Cancer Center, Clinical Cancer Genetics Laboratory, New York, NY 10065;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Offit","sequence":"additional","affiliation":[{"name":"Memorial Sloan-Kettering Cancer Center, Clinical Cancer Genetics Laboratory, New York, NY 10065;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry","family":"Lynch","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine, Creighton University School of Medicine, Omaha, NE 68178;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter H.","family":"Wiernik","sequence":"additional","affiliation":[{"name":"Our Lady of Mercy Cancer Center, New York Medical College, Bronx, NY 10466; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikhail","family":"Roshal","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, University of Washington School of Medicine, Seattle, WA 98195;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary Lou","family":"McMaster","sequence":"additional","affiliation":[{"name":"Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret","family":"Tucker","sequence":"additional","affiliation":[{"name":"Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan R.","family":"Fromm","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, University of Washington School of Medicine, Seattle, WA 98195;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynn R.","family":"Goldin","sequence":"additional","affiliation":[{"name":"Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marshall S.","family":"Horwitz","sequence":"additional","affiliation":[{"name":"Department of Pathology,"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2009,9]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-12-4750"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pathol.1.110304.100209"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.20189"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2004.027433"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.424728"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1651562"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1556\/amicr.49.2002.1.7"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-03-3253"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.6.3042"},{"key":"e_1_3_3_10_2","first-page":"5365","article-title":"High frequency of chromosome 3p deletion in histologically normal nasopharyngeal epithelia from southern Chinese","volume":"60","author":"Chan AS","year":"2000","unstructured":"AS Chan, et al., High frequency of chromosome 3p deletion in histologically normal nasopharyngeal epithelia from southern Chinese. 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