HCL highly stable genomic profile; however, BRAF V600E somatic mutation, found in all classic HCL, which does not explain all morphologic, phenotypic, and immunogenetic features of HCL.

Authors investigated genome-wide promoter methylation of series of classical HCL, hypothesizing that epigenetic changes might contribute to pathogenesis of disease.

Authors revealed 2 main clusters: one contained HCL, SMZL and NBCs, while other contained CLL samples. In particular, methylation status at non-CGI CpG residues able to reveal HCL as separate cluster.

HCL had genome-wide promoter methylation profile distinct from other lymphoprolipherative disorders.

HCL showed methylation differences in promoter regions of genes associated with migration/homing (CXCR5), proliferation (CDKN2B, VHL), DNA repair (MGMT), and apoptosis (NOXA, TRAILR1).