Refinement of 1p36 Alterations Not Involving PRDM16 in Myeloid and Lymphoid Malignancies

Abstract

Fluorescence in situ hybridization was performed to characterize 81 cases of myeloid and lymphoid malignancies with cytogenetic 1p36 alterations not affecting the PRDM16 locus. In total, three subgroups were identified: balanced translocations (N = 27) and telomeric rearrangements (N = 15), both mainly observed in myeloid disorders; and unbalanced non-telomeric rearrangements (N = 39), mainly observed in lymphoid proliferations and frequently associated with a highly complex karyotype. The 1p36 rearrangement was isolated in 12 cases, mainly myeloid disorders. The breakpoints on 1p36 were more widely distributed than previously reported, but with identifiable rare breakpoint cluster regions, such as the TP73 locus. We also found novel partner loci on 1p36 for the known multi-partner genes HMGA2 and RUNX1. We precised the common terminal 1p36 deletion, which has been suggested to have an adverse prognosis, in B-cell lymphomas [follicular lymphomas and diffuse large B-cell lymphomas with t(14;18)(q32;q21) as well as follicular lymphomas without t(14;18)]. Intrachromosomal telomeric repetitive sequences were detected in at least half the cases of telomeric rearrangements. It is unclear how the latter rearrangements occurred and whether they represent oncogenic events or result from chromosomal instability during oncogenesis.

PRDM16 (1p36) translocations define a distinct entity of myeloid malignancies with poor prognosis but may also occur in lymphoid malignancies

“…PRDM16 was the most commonly rearranged locus in our study of 1p36 abnormalities, as it was involved in 39 out of 120 patients with haematological malignancies (Duhoux et al , 2011), representing the largest series of cases with PRDM16 rearrangements published so far. Apparently balanced translocations involving PRDM16 can be subdivided into two distinct categories according to their functional consequences: either the deregulation of an oncogene or the formation of a chimeric gene.…”

Autologous Adipose Stromal Cells Seeded onto a Human Collagen Matrix for Dermal Regeneration in Chronic Wounds

“…Chromosome harvesting and metaphase slide preparation were performed according to standard procedures. 25 Eleven to 20 reverse trypsin Wright G-banded metaphases were analyzed and karyotypes were reported according to the 2013 International System for Human Cytogenetics Nomenclature. Fluorescent in situ hybridization analysis was performed according to standard protocols 25 to detect aneuploidy of chromosomes 5, 7, 8, and 18 using TelVysion 5q (SpectrumOrange; Abbot Molecular, Ottignies/Louvain-la-Neuve, Belgium), CEP7/D7Z1 (SpectrumGreen or SpectrumOrange; Abbot Molecular), CEP8/D8Z2 (SpectrumOrange or SpectrumGreen), and CEP18/D18Z1 (SpectrumGreen) probes.…”

“…25 Eleven to 20 reverse trypsin Wright G-banded metaphases were analyzed and karyotypes were reported according to the 2013 International System for Human Cytogenetics Nomenclature. Fluorescent in situ hybridization analysis was performed according to standard protocols 25 to detect aneuploidy of chromosomes 5, 7, 8, and 18 using TelVysion 5q (SpectrumOrange; Abbot Molecular, Ottignies/Louvain-la-Neuve, Belgium), CEP7/D7Z1 (SpectrumGreen or SpectrumOrange; Abbot Molecular), CEP8/D8Z2 (SpectrumOrange or SpectrumGreen), and CEP18/D18Z1 (SpectrumGreen) probes. Two hundred nuclei were counted for passage 1, passage 4, and passage 16; 120 nuclei were counted for passage 10; and 73 nuclei were counted for passage 12 (the thresholds were calculated following the beta law with a confidence interval of 99.9 percent).…”

Early lesions of follicular lymphoma: a genetic perspective

“…Ten genes in shared losses were recognized tumor suppressor genes (Online Supplementary Tables S2 and S3), including TP73, 36 also deleted in DFL, 50% of FL, and transcriptionally down-regulated in large cohorts of FL (Online Supplementary Figure S6). While several of the amplified oncogenes have been previously associated with FL, to our knowledge only few of the deleted tumor suppressors have yet been reported as recurrent events or functionally involved in FL pathogenesis and/or lymphomagenesis, and we cannot exclude that some might correspond to passenger alterations.…”