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.