Distinct age-associated molecular profiles in acute myeloid leukemia defined by comprehensive clinical genomic profiling.

Distinct age-associated molecular profiles in acute myeloid leukemia defined by comprehensive clinical genomic profiling. Oncotarget. 2018 May 29;9(41):26417-26430 Authors: Tarlock K, Zhong S, He Y, Ries R, Severson E, Bailey M, Morley S, Balasubramanian S, Erlich R, Lipson D, Otto GA, Vergillo JA, Kolb EA, Ross JS, Mughal T, Stephens PJ, Miller V, Meshinchi S, He J Abstract Large scale comprehensive genomic profiling (CGP) has led to an improved understanding of oncogenic mutations in acute myeloid leukemia (AML), as well as identification of alterations that can serve as targets for potential therapeutic intervention. We sought to gain insight into age-associated variants in AML through comparison of extensive DNA and RNA-based GP results from pediatric and adult AML. Sequencing of 932 AML specimens (179 pediatric (age 0-18), 753 adult (age ≥ 19)) from diagnostic, relapsed, and refractory times points was performed. Comprehensive DNA (405 genes) and RNA (265) sequencing to identify a variety of structural and short variants was performed. We found that structural variants were highly prevalent in the pediatric cohort compared to the adult cohort (57% vs. 30%; p < 0.001), with certain structural variants detected only in the pediatric cohort. Fusions were the most common structural variant and were highly prevalent in AML in very young children occurring in 68% of children < 2 years of age. We observed an inverse trend in th...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research