GAB2 is a novel target of 11q amplification in AML/MDS.
Chromosome arm 11q amplifications involving the mixed lineage leukemia gene (MLL) locus are rare but recurrent aberrations in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). We have recently shown that in addition to the MLL core amplicon, independent sequences in 11q23-24 and/or 11q13.5 are coamplified within the same cytogenetic markers in 90% and 60% of patients, respectively. Here we further narrow down the minimal amplicon in 11q13.5 to 1.17 Mb by means of semi-quantitative PCR and FISH analyses. The newly defined amplicon contains seven genes, including the GRB2-associated binding protein 2 (GAB2). Using real-time RT-PCR we show a significant transcriptional upregulation of GAB2 in the patients who have GAB2 coamplified with MLL. Thus, the adaptor molecule GAB2 that has already been shown to enhance oncogenic signaling in other neoplasias appears as a novel target of 11q amplification in AML/MDS.
Zatkova
Andrea
A
Abteilung für Humangenetik, Klinisches Institut für Medizinische und Chemische Labor Diagnostik (KIMCL), Medizinische Universität Wien, Währinger Strasse 10, A-1090 Vienna, Austria. andrea.zatkova@meduniwien.ac.at
Schoch
Claudia
C
Speleman
Frank
F
Poppe
Bruce
B
Mannhalter
Christine
C
Fonatsch
Christa
C
Wimmer
Katharina
K
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D002880:Chromosomes, Human, Pair 11; D005260:Female; D005784:Gene Amplification / Q000502:physiology*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000235:genetics*
D048868:Adaptor Proteins, Signal Transducing; C490895:GAB2 protein, human