Novel coding and noncoding gene variants have been identified that may increase the risk for developing Hodgkin lymphoma (HL), according to a study published in Blood. Jamie E. Flerlage, MD, MS, and colleagues performed whole-genome sequencing on 234 individuals with and without HL from 36 pedigrees with two or more first-degree relatives with HL. To identify coding and noncoding variants, a family-based segregation analysis was performed. Forty-four HL risk variants in 28 pedigrees were identified, of which 33 and 11 were coding and noncoding, respectively. The top four recurrent risk variants were a coding variant in KDR, a 5’UTR in KLHDC8B, and noncoding variants in an intron of PAX5 and in an intron of GATA3. For one pedigree, a newly identified splice variant in KDR and high confidence stop gain variants affecting IRF7 and EEF2KMT were seen. In three independent pedigrees, multiple truncating variants in POLR1E were observed. “We married several existing tools as well as customized approaches to make a pipeline that could process data from these families in a meaningful way,” a co-author said in a statement.
