Amplified, lost, and fused genes in 11q23-25 amplicon in acute myeloid leukemia, an array-CGH study.
Gene amplifications occur rarely in hematologic neoplasms. We characterized two cases of acute myeloid leukemia (AML) with marker chromosomes and 11q23-25 amplicons. Case 1 was a 14-year-old male with an additional ring of chromosome 11 material as the sole karyotypic abnormality, as determined by G-banding and multicolor fluorescence in situ hybridization. Standard comparative genomic hybridization (CGH) showed amplification in 11q23-qter. However, the MLL gene, in 11q23, was not amplified by FISH. Case 2 was a 38-year-old male with the G-banding karyotype 51,XY,+8,+19,+3mar and with 11q22-qter amplification by standard CGH. This patient also had the MLL-LARG fusion gene. We used microarray-based CGH (array-CGH) to characterize the amplicons. In case 1, the amplified region in 11q24.3-25 (5.5 Mb) was continuous, and MLL was not amplified, as expected. In case 2, the amplicon was divided into two distinct parts, in 11q23.3 (1.2 Mb) and in 11q23.3-25 (13.3 Mb). It contained a loss ( approximately 1 Mb) in 11q23.3, and the amplicon breakpoint was in the middle of MLL. Although the amplicon size varied, the patients had a common amplified region in 11q24-25 that comprised 14 genes. Expression microarray of case 1 revealed that three of these genes, FLI1, NFRKB, and SNX19, were also overexpressed. The results indicate that the 11q24-q25 region may harbor new candidate oncogenes. In addition, the complex amplicon of case 2 suggests some intriguing chromosomal mechanisms.
Tyybäkinoja
Anne
A
Department of Pathology, Haartman Institute and HUSLAB, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
Saarinen-Pihkala
Ulla
U
Elonen
Erkki
E
Knuutila
Sakari
S
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D002869:Chromosome Aberrations; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005784:Gene Amplification; D017353:Gene Deletion; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics*; D008297:Male; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D009857:Oncogenes; D051789:Proto-Oncogene Protein c-fli-1 / Q000235:genetics / Q000378:metabolism
D004268:DNA-Binding Proteins; C497422:KMT2A protein, human; C072725:NFRKB protein, human; D051789:Proto-Oncogene Protein c-fli-1; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase