KLHDC8B in Hodgkin lymphoma and possibly twinning

A key feature of Hodgkin lymphoma is that the malignant cells are binucleated, as a consequence of failed cytokinesis. We recently ascertained a family in which multiple cases of Hodgkin lymphoma had occurred among individuals who inherited a balanced chromosomal translocation. We cloned the translocation breakpoints and found that it disrupted a previously uncharacterized gene, KLHDC8B, encoding a Kelch family protein whose deficiency impairs cytokinesis and leads to binucleated cells. In other families we found a rare single nucleotide polymorphism affecting mitotic translation of KLHDC8B that was associated with and linked to Hodgkin lymphoma. Interestingly, the index family demonstrated an unusual frequency of twins, and there is a previously reported association between Hodgkin lymphoma and twins. Here we review the unusual genetic features of Hodgkin lymphoma, including gender concordance among siblings, and genetically test the hypothesis that KLHDC8B may participate in twinning by disrupting cytokinesis through impediment of polar body separation from oocytes.