Evaluating a CLL susceptibility variant in ITGB2 in families with multiple sub-types of hematological malignancies

The application of rapid and affordable genome sequencing technologies to families with a high incidence of hematological malignancies (HMs) provides significant opportunities for understanding the genetic causes of these cancers. In one of the few studies published to date using this approach, Goldin et al recently reported that a rare variant (rs2230531) within ITGB2 is associated with genetic predisposition to chronic lymphocytic leukemia (CLL). In this study whole exome sequencing (WES) was performed in a discovery set of 20 high-risk CLL families. Analysis proceeded on a ‘per family basis’, to identify rare (minor allele frequency (MAF) < 1% in population databases), nonsynonymous variants shared in the CLL cases, as well as obligate carriers and non-Hodgkin lymphoma (NHL) cases. In 20 families, 926 variants were prioritized, of which two were identified in multiple families, rs2230531 in ITGB2 and rs201725177 in SWI5.