Most of the exons with extremely high coverage (>1400X) appeared to come from a few genes [HYDIN, axonemal central pair apparatus protein (HYDIN) and lysine (K)specific methyltransferase 2C (KMT2C, also known as MLL3
)] and were likely caused by incompleteness (homologous regions not represented) in the hg19 reference genome (see online Supplemental Table 4); we therefore excluded mutations detected in those exons.
As the majority of cases over-expressing HOXA9 in the study exhibited bi-allelic expression, consistent with deregulation of an upstream HMT event, genes involved in regulating HOXA9 were evaluated for mutations with findings revealing mutations in several genes: MLL, MLL2, MLL3
, and MMSET .
The TrxG core interacts with a group of interchangeable H3K4 methyltransferases, including some called mixed lineage leukemia (MLL) proteins (i.e., MLL1, MLL2, MLL3
, and MLL4) and proteins called SET1A and SET1B (Jiang et al.
Mutations in MLL2 and MLL3
were identified in 16 percent of the entire set of 88 medulloblastoma samples.