Mutations in a gene encoding a midbody protein in binucleated Reed-Sternberg cells of Hodgkin lymphoma.
Classical Hodgkin lymphoma (cHL) is a cancer in which malignant "Reed-Sternberg" cells comprise just a fraction of the bulk of the tumor and are characteristically binucleated. We recently identified a novel gene, KLHDC8B, which appears responsible for some familial cases of cHL. KLHDC8B encodes a midbody kelch protein expressed during cytokinesis. Deficiency of KLHDC8B leads to binucleated cells, implicating its involvement in Reed-Sternberg cell formation. Interestingly, other cancer genes, such as BRCA1 and BRCA2, also encode proteins locating to the midbody during cytokinesis, even though their participation in other pathways has received greater attention. Midbody components may be an overlooked source of tumor suppressor genes.
Krem
Maxwell M
MM
Medical Oncology Program, Institute for Stem Cell & Regenerative Medicine, University of Washington, Seattle, WA, USA.
Salipante
Stephen J
SJ
Horwitz
Marshall S
MS
D019313:BRCA1 Protein / Q000378:metabolism; D024682:BRCA2 Protein / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D048749:Cytokinesis; D006367:HeLa Cells; D006689:Hodgkin Disease / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D009154:Mutation; D016539:Reed-Sternberg Cells / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
D019313:BRCA1 Protein; D024682:BRCA2 Protein; D018797:Cell Cycle Proteins; C549813:KLHDC8B protein, human; D025521:Tumor Suppressor Proteins; C102449:BARD1 protein, human; D044767:Ubiquitin-Protein Ligases