Chromosome 20 deletions in myelodysplastic syndromes and Philadelphia-chromosome-negative myeloproliferative disorders: characterization by molecular cytogenetics of commonly deleted and retained regions

Abstract

Deletion of the long arm of chromosome 20 is a recurrent abnormality observed in myelodysplastic syndromes (MDS) and in Philadelphia-chromosome-negative myeloproliferative disorders (MPD). Our objective was to characterize the deletion size among 38 MDS and MPD patients using fluorescence in situ hybridization (FISH) with bacterial artificial chromosome (BAC) probes and to define commonly deleted and retained regions on chromosome 20. Patients were distributed in three groups according to the World Health Organization classification: MDS (22 patients), MPD (12 patients) and myelodysplastic/myeloproliferative diseases (four patients). FISH with centromeric, subtelomeric, and unique sequence probes was performed to characterize the deletion whereas its size was delineated using BAC clones. All 38 deletions were found to be interstitial. A commonly deleted region was identified for each of the three groups; it varied from 6.62 to 10.4 Mb and showed considerable overlapping. Two commonly retained regions (CRR), also showing overlapping, were identified in all three groups, one in the centromeric region, the other in the telomeric region. The deletion size is highly variable, with no apparent recurrent breakpoint. The deletion may result in the loss of one or several tumor suppressor genes but the target genes remain unknown. Loss of genes plays an important part in the myeloid leukemic process associated with del(20q). However, genes located in the retained chromosomal regions may also play a role in the oncogenetic mechanisms.

Clonal analysis of deletions on chromosome 20q and JAK2-V617F in MPD suggests that del20q acts independently and is not one of the predisposing mutations for JAK2-V617F

“…11 In MPD patients, del20q was found in the bone marrow from approximately 1% of patients with essential thrombocythemia (ET), up to 9% of polycythemia vera (PV) and up to 12% of primary myelofibrosis (PMF). 10,12 The del20q occurred preferentially together with the JAK2-V617F mutation in 28 of 29 MPD patients studied. 13 We previously analyzed 2 such patients with del20q and JAK2-V617F and found that the size of the del20q clone by far exceeded the size of the clone carrying JAK2-V617F, 14 suggesting that del20q preceded the acquisition of the JAK2-V617F mutation.…”

“…[1][2][3][4] A common deleted region (CDR) of 2.7 megabases (Mb) was mapped for patients with MPD, and a 2.6-Mb CDR was defined for MDS/AML with an overlap of 1.7 Mb between the 2 CDRs. [5][6][7][8][9][10] However, to date, it was not possible to identify a gene mutation within the CDR that is functionally linked to the expansion of the del20q clone. 11 In MPD patients, del20q was found in the bone marrow from approximately 1% of patients with essential thrombocythemia (ET), up to 9% of polycythemia vera (PV) and up to 12% of primary myelofibrosis (PMF).…”

Dido mutations trigger perinatal death and generate brain abnormalities and behavioral alterations in surviving adult mice

“…Misregulation of the dido gene is linked to increased incidence of genomic instability, myelodysplasia, and myeloproliferation, melanoma, and infertility (13,17,26,28). Elucidating the mechanisms that govern the complex activities could help clarify the role of Dido in promoting stem cell differentiation, cilia size, tumorigenesis and, as shown here, life expectancy, brain development, and neural behavior alterations.…”

Cytogenetic Evaluation in 221 Untreated Patients with Myelodysplastic Syndrome

“…However, there are also studies where no significant difference in median survival has been observed between patients with +8 as a single abnormality and patients with +8 associated with another cytogenetic abnormality. 7,10,13,[35][36][37][38] In our study, there were 10 patients with trisomy 8. In three of them, trisomy 8 was the only abnormality, in another three there was an additional abnormality and in four, a complex karyotype was detected.…”