High-Throughput Mutation Analysis of Tyrosine Kinome in Childhood AML

Childhood AML resembles 20% off all acute leukemias with only a 60% survival rate. In the past years, numerous of the 518 members of the kinase gene family have been shown to play a major role in multiple malignant diseases including leukemia. Initial resequencing studies using conventional resequencing have been performed on the kinase family to identify somatic mutations, representing an enormous effort in cost and labor. Recently, next-generation sequencing technologies opened the path to analyze larger portions of the human genome in a less time consuming manner.

Combining array-based sequence specific sequence capture for the exons of all human kinases and massively parallelized pyrosequencing, we resequenced the kinomes of two patients with acute myeloic leukemia, yielding approximately 190 megabases of mappable reads with 1700+ initial high-confidence differences per patient. Here we present our resequencing data and our efforts in interpreting these data.