ASXL1 and neoplasm: The second confidently identified driver mutation was a frameshift mutation in exon 12 of ASXL1. ASXL1 is a known tumor suppressor in hematological malignancies, where the majority of frameshift and nonsense mutations are also observed in exon 12.26, 27 ASXL1 loss leads to loss of H3K27me3 and increased expression of genes repressed by these histone marks, especially the anterior HOXA gene cluster.24 HOXA genes themselves are capable of leukemogenic transformation.31 Interestingly, we also observe a concomitant and specific amplification of the HOXA gene cluster in this tumor.