Limits...
Refinement of 1p36 alterations not involving PRDM16 in myeloid and lymphoid malignancies.

Duhoux FP, Ameye G, Lambot V, Herens C, Lambert F, Raynaud S, Wlodarska I, Michaux L, Roche-Lestienne C, Labis E, Taviaux S, Chapiro E, Nguyen-Khac F, Khac FN, Struski S, Dobbelstein S, Dastugue N, Lippert E, Speleman F, Van Roy N, De Weer A, Rack K, Talmant P, Richebourg S, Mugneret F, Tigaud I, Mozziconacci MJ, Laibe S, Nadal N, Terré C, Libouton JM, Decottignies A, Vikkula M, Poirel HA, Groupe Francophone de Cytogénétique Hématologique (GFCH)Belgian Cytogenetic Group for Hematology and Oncology (BCG-H - PLoS ONE (2011)

Bottom Line: We also found novel partner loci on 1p36 for the known multi-partner genes HMGA2 and RUNX1.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.

View Article: PubMed Central - PubMed

Affiliation: Center for Human Genetics, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium.

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.

Show MeSH

Related in: MedlinePlus

Telomeric rearrangements.Schematic representation of the probes used and of the findings in the cases of telomeric rearrangements. The sub-telomeric probe TelVysion 1p ® is represented in green, the pan-telomeric probe Star*FISH© in red. Material from chromosome 1 is represented in white and the additional material is shaded. A: normal pattern; B: the sub-telomeric and pan-telomeric probes are retained in a centromeric position to the additional material (7 cases); C: only the sub-telomeric probe is retained in a centromeric position to the additional material (6 cases); D: the sub-telomeric probe is present and the presence of the pan-telomeric probe cannot be evaluated due to the resolution of the FISH probes (2 cases): given the shortness of the additional material, it is impossible to assess whether the signal seen with the pan-telomeric probe corresponds to the signal seen in all cases at the telomeric end of the derivative chromosomes, or whether it corresponds to the juxtaposition of this telomeric signal with an intra-chromosomal signal. Additional FISH results are available in Table S4.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3198844&req=5

pone-0026311-g004: Telomeric rearrangements.Schematic representation of the probes used and of the findings in the cases of telomeric rearrangements. The sub-telomeric probe TelVysion 1p ® is represented in green, the pan-telomeric probe Star*FISH© in red. Material from chromosome 1 is represented in white and the additional material is shaded. A: normal pattern; B: the sub-telomeric and pan-telomeric probes are retained in a centromeric position to the additional material (7 cases); C: only the sub-telomeric probe is retained in a centromeric position to the additional material (6 cases); D: the sub-telomeric probe is present and the presence of the pan-telomeric probe cannot be evaluated due to the resolution of the FISH probes (2 cases): given the shortness of the additional material, it is impossible to assess whether the signal seen with the pan-telomeric probe corresponds to the signal seen in all cases at the telomeric end of the derivative chromosomes, or whether it corresponds to the juxtaposition of this telomeric signal with an intra-chromosomal signal. Additional FISH results are available in Table S4.

Mentions: There were 15 patients with rearrangements located at the extreme telomeric end of chromosomal band 1p36.33, as identified with the sub-telomeric 1p probe and the pan-telomeric probe. The additional chromosomal material was located (i) telomerically to the canonical repetitive telomeric sequences on the derivative chromosome 1p in at least 7 cases (Figure 4B), (ii) between the sub-telomeric 1p region and the first 3.5 kb of the repetitive telomeric region in 6 cases (Figure 4C), (iii) while in 2 further cases, the possible presence of intrachromosomal telomeric repetitive sequences could not be assessed due to an insufficient length of the additional material (Figure 4D). Eleven out of 15 patients from this subgroup had myeloid [5 AML, 2 MDS, 1 PV, 1 MF, 1 chronic eosinophilic leukemia (CEL) and 1 Fanconi's anemia (FA)] and 4/15 had lymphoid malignancies [1 B-cell ALL, 2 mantle cell lymphomas (MCL) and 1 TCL]. Although the bone marrow was morphologically normal, the case of FA (patient 125) had acquired a subclonal add(1)(p36) in addition to a previously identified gain of the long arm of chromosome 1, suggesting the clonal evolution towards a hematological malignancy. Results of FISH analysis are depicted in Figure 4 and in Table S4.


Refinement of 1p36 alterations not involving PRDM16 in myeloid and lymphoid malignancies.

Duhoux FP, Ameye G, Lambot V, Herens C, Lambert F, Raynaud S, Wlodarska I, Michaux L, Roche-Lestienne C, Labis E, Taviaux S, Chapiro E, Nguyen-Khac F, Khac FN, Struski S, Dobbelstein S, Dastugue N, Lippert E, Speleman F, Van Roy N, De Weer A, Rack K, Talmant P, Richebourg S, Mugneret F, Tigaud I, Mozziconacci MJ, Laibe S, Nadal N, Terré C, Libouton JM, Decottignies A, Vikkula M, Poirel HA, Groupe Francophone de Cytogénétique Hématologique (GFCH)Belgian Cytogenetic Group for Hematology and Oncology (BCG-H - PLoS ONE (2011)

Telomeric rearrangements.Schematic representation of the probes used and of the findings in the cases of telomeric rearrangements. The sub-telomeric probe TelVysion 1p ® is represented in green, the pan-telomeric probe Star*FISH© in red. Material from chromosome 1 is represented in white and the additional material is shaded. A: normal pattern; B: the sub-telomeric and pan-telomeric probes are retained in a centromeric position to the additional material (7 cases); C: only the sub-telomeric probe is retained in a centromeric position to the additional material (6 cases); D: the sub-telomeric probe is present and the presence of the pan-telomeric probe cannot be evaluated due to the resolution of the FISH probes (2 cases): given the shortness of the additional material, it is impossible to assess whether the signal seen with the pan-telomeric probe corresponds to the signal seen in all cases at the telomeric end of the derivative chromosomes, or whether it corresponds to the juxtaposition of this telomeric signal with an intra-chromosomal signal. Additional FISH results are available in Table S4.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3198844&req=5

pone-0026311-g004: Telomeric rearrangements.Schematic representation of the probes used and of the findings in the cases of telomeric rearrangements. The sub-telomeric probe TelVysion 1p ® is represented in green, the pan-telomeric probe Star*FISH© in red. Material from chromosome 1 is represented in white and the additional material is shaded. A: normal pattern; B: the sub-telomeric and pan-telomeric probes are retained in a centromeric position to the additional material (7 cases); C: only the sub-telomeric probe is retained in a centromeric position to the additional material (6 cases); D: the sub-telomeric probe is present and the presence of the pan-telomeric probe cannot be evaluated due to the resolution of the FISH probes (2 cases): given the shortness of the additional material, it is impossible to assess whether the signal seen with the pan-telomeric probe corresponds to the signal seen in all cases at the telomeric end of the derivative chromosomes, or whether it corresponds to the juxtaposition of this telomeric signal with an intra-chromosomal signal. Additional FISH results are available in Table S4.
Mentions: There were 15 patients with rearrangements located at the extreme telomeric end of chromosomal band 1p36.33, as identified with the sub-telomeric 1p probe and the pan-telomeric probe. The additional chromosomal material was located (i) telomerically to the canonical repetitive telomeric sequences on the derivative chromosome 1p in at least 7 cases (Figure 4B), (ii) between the sub-telomeric 1p region and the first 3.5 kb of the repetitive telomeric region in 6 cases (Figure 4C), (iii) while in 2 further cases, the possible presence of intrachromosomal telomeric repetitive sequences could not be assessed due to an insufficient length of the additional material (Figure 4D). Eleven out of 15 patients from this subgroup had myeloid [5 AML, 2 MDS, 1 PV, 1 MF, 1 chronic eosinophilic leukemia (CEL) and 1 Fanconi's anemia (FA)] and 4/15 had lymphoid malignancies [1 B-cell ALL, 2 mantle cell lymphomas (MCL) and 1 TCL]. Although the bone marrow was morphologically normal, the case of FA (patient 125) had acquired a subclonal add(1)(p36) in addition to a previously identified gain of the long arm of chromosome 1, suggesting the clonal evolution towards a hematological malignancy. Results of FISH analysis are depicted in Figure 4 and in Table S4.

Bottom Line: We also found novel partner loci on 1p36 for the known multi-partner genes HMGA2 and RUNX1.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.

View Article: PubMed Central - PubMed

Affiliation: Center for Human Genetics, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium.

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.

Show MeSH
Related in: MedlinePlus