Distinct sequences on 11q13.5 and 11q23-24 are frequently coamplified withMLL in complexly organized 11q amplicons in AML/MDS patients

Autor: Reinhard Ullmann, Christa Fonatsch, Sam M. Hanash, Susanne Schnittger, Andrea Zatkova, Claudia Schoch, Barbara J. Lamb, Rork Kuick, Jean Marie Rouillard, Katharina Wimmer
Rok vydání: 2004
Předmět:
Genetic Markers
Male
Cancer Research
Restriction Mapping
Restriction landmark genomic scanning
Gene Dosage
Locus (genetics)
Biology
Polymerase Chain Reaction
hemic and lymphatic diseases
Proto-Oncogenes
Genetics
medicine
Humans
neoplasms
In Situ Hybridization
Fluorescence
Aged
Oligonucleotide Array Sequence Analysis
Aged
80 and over
medicine.diagnostic_test
Chromosomes
Human
Pair 11
Gene Amplification
Nucleic Acid Hybridization
Myeloid leukemia
DNA
Neoplasm
Histone-Lysine N-Methyltransferase
Middle Aged
Amplicon
Molecular biology
DNA-Binding Proteins
Leukemia
Myeloid
Myelodysplastic Syndromes
Chromosome Arm
Acute Disease
Cytogenetic Analysis
Chromosomal region
Female
DNA Probes
Myeloid-Lymphoid Leukemia Protein
Transcription Factors
Fluorescence in situ hybridization
Comparative genomic hybridization
Zdroj: Genes, Chromosomes and Cancer. 39:263-276
ISSN: 1098-2264
1045-2257
DOI: 10.1002/gcc.20002
Popis: Amplification within chromosome arm 11q involving the mixed-lineage leukemia gene (MLL) locus is a rare but recurrent aberration in acute myeloid leukemia and myelodysplastic syndrome (AML/MDS). We and others have observed that 11q amplifications in most AML/MDS cases have not been restricted to the chromosomal region surrounding the MLL gene. Therefore, we implemented a strategy to characterize comprehensively 11q amplicons in a series of 13 AML/MDS patients with MLL amplification. Analysis of 4 of the 13 cases by restriction landmark genomic scanning in combination with virtual genome scan and by matrix-based comparative genomic hybridization demonstrated that the 11q amplicon in these four cases consisted of at least three discontinuous sequences derived from different regions of the long arm of chromosome 11. We defined a maximally 700-kb sequence around the MLL gene that was amplified in all cases. Apart from the core MLL amplicon, we detected two additional 11q regions that were coamplified. Using fluorescence in situ hybridization (FISH) analysis, we demonstrated that sequences in 11q13.5 and 11q23–24 were amplified in 8 of 13 and 10 of 12 AML/MDS cases, respectively. Both regions harbor a number of potentially oncogenic genes. In all 13 cases, either one or both of these regions were coamplified with the MLL amplicon. Thus, we demonstrated that 11q amplicons in AML/MDS patients display a complex organization and have provided evidence for coamplification of two additional regions on the long arm of chromosome 11 that may harbor candidate target genes. © 2004 Wiley-Liss, Inc.
Databáze: OpenAIRE
Externí odkaz: