Analysis of myelodysplastic syndromes with complex karyotypes by high-resolution comparative genomic hybridization and subtelomeric CGH array.
Molecular cytogenetic techniques enabled us to clarify numerical and structural alterations previously detected by conventional cytogenetic techniques in 37 patients who had myelodysplastic syndromes with complex karyotypes. Using high-resolution comparative genomic hybridization (HR-CGH), we found the most recurrent alterations to be deletion of 5q (70%), 18q (35%), 7q (32%), 11q (30%), and 20q (24%), gain of 11q (35%) and 8q (24%), and trisomy of chromosome 8 (19%). Furthermore, in 35% of the patients, 20 amplifications were identified. These amplifications were shown by FISH to involve some genes previously described as amplified in hematological malignancies, such as ERBB2, MLL, and RUNX1. In addition, two other genes, BCL6 and BCL2, which are classically related to apoptosis and non-Hodgkin lymphoma, were shown for the first time to be involved in amplification. Genomic alterations involving different subtelomeric regions with losses in 4p16, 5p15.3, 6q27, 18p11.3, and 18q23 and gains in 1p36.3 and 19p13.3 were detected by HR-CGH. Array CGH analysis of the subtelomeric regions in some samples was able to confirm a number of these alterations and found some additional alterations not detected by conventional CGH.
Martínez-Ramírez
Angel
A
Department of Human Genetics, Spanish National Cancer Centre (CNIO), Madrid, Spain.
Urioste
Miguel
M
Melchor
Lorenzo
L
Blesa
David
D
Valle
Laura
L
de Andrés
Sara Alvarez
SA
Kok
Klaas
K
Calasanz
Maria José
MJ
Cigudosa
Juan Cruz
JC
Benítez
Javier
J
D000368:Aged; D000369:Aged, 80 and over; D002869:Chromosome Aberrations; D022202:Chromosomes, Artificial, Bacterial / Q000235:genetics; D002877:Chromosomes, Human / Q000235:genetics*; D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D018734:Genes, erbB-2 / Q000235:genetics; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D007621:Karyotyping; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000235:genetics*; D051788:Myeloid-Lymphoid Leukemia Protein; D009693:Nucleic Acid Hybridization; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2; D051560:Proto-Oncogene Proteins c-bcl-6; D011519:Proto-Oncogenes / Q000235:genetics; D016615:Telomere / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics
D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins; C497422:KMT2A protein, human; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051560:Proto-Oncogene Proteins c-bcl-6; C493728:RUNX1 protein, human; D014157:Transcription Factors; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase