High-resolution genomic profiling of adult and pediatric core-binding factor acute myeloid leukemia reveals new recurrent genomic alterations
Year: 2012
Type: article
Study design: Observational Study
Abstract: To identify cooperating lesions in core-binding factor acute myeloid leukemia, we performed single-nucleotide polymorphism-array analysis on 300 diagnostic and 41 relapse adult and pediatric leukemia samples. We identified a mean of 1.28 copy number alterations per case at diagnosis in both patient populations. Recurrent minimally deleted regions (MDRs) were identified at 7q36.1 (7.7%), 9q21.32 (5%), 11p13 (2.3%), and 17q11.2 (2%). Approximately one-half of the 7q deletions were detectable only by single-nucleotide polymorphism-array analysis because of their limited size. Sequence analysis of MLL3, contained within the 7q36.1 MDR, in 46 diagnostic samples revealed one truncating mutation in a leukemia lacking a 7q deletion. Recurrent focal gains were identified at 8q24.21 (4.7%) and 11q25 (1.7%), both containing a single noncoding RNA. Recurrent regions of copy-neutral loss-of-heterozygosity were identified at 1p (1%), 4q (0.7%), and 19p (0.7%), with known mutated cancer genes present in the minimally altered region of 1p (NRAS) and 4q (TET2). Analysis of relapse samples identified recurrent MDRs at 3q13.31 (12.2%), 5q (4.9%), and 17p (4.9%), with the 3q13.31 region containing only LSAMP, a putative tumor suppressor. Determining the role of these lesions in leukemogenesis and drug resistance should provide important insights into core-binding factor acute myeloid leukemia.
Source: Blood
Authors: Michael W. M. Kühn, Ina Radtke, Lars Bullinger, Salil Goorha, Jinjun Cheng, Jennifer Edelmann, Juliane Gohlke, Xiaoping Su, Peter Paschka, Stanley Pounds, Jürgen Krauter, Arnold Ganser, Asmaa Quessar, Raul Ribeiro, Verena I. Gaidzik, Sheila Shurtleff, Jan Krönke, Karlheinz Holzmann, Jing Ma, Richard F. Schlenk, Jeffrey E. Rubnitz, Konstanze Döhner, Hartmut Döhner, James R. Downing
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funder: National Cancer Institute
OpenAlex ID: W2093601292