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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.

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TP73 rearrangements.Schematic representation of the position of BAC probes and loci of interest in patients 050, 008, 141 and 105 (patients with TP73 involvement), adapted from www.ensembl.org. Due to lack of material, the partner locus could not be determined in the case of patient 105. Of note, in patients 050 and 105, given the FISH resolution, we could not rule out an involvement of the WRAP73 locus, which is a member of the WD repeat family, involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation [53].
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pone-0026311-g002: TP73 rearrangements.Schematic representation of the position of BAC probes and loci of interest in patients 050, 008, 141 and 105 (patients with TP73 involvement), adapted from www.ensembl.org. Due to lack of material, the partner locus could not be determined in the case of patient 105. Of note, in patients 050 and 105, given the FISH resolution, we could not rule out an involvement of the WRAP73 locus, which is a member of the WD repeat family, involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation [53].

Mentions: No obvious hotspot could be identified except for 2 recurring breakpoints, defined as 2 or more cases harboring the same breakpoint. The first occurred within the TP73 locus, in which two breakpoint patterns were observed (Figure 2): the breakpoint was either between probes RP11-46F15 and RP5-1092A11 in patients 050 and 105, or within the latter probe in patients 008 and 141. In patient 050, the BAC pattern on 9q22.2 suggested an involvement of the CKS2 (a cell cycle regulator [26]), the SECISBP2 or the SEMA4D locus. Due to lack of material, the partner locus of patient 105 could not be identified. In patient 008, the partner locus of TP73 was located in a 3 Mb region on 2q22. Finally, in patient 141, there were 2 balanced translocations, both affecting the TP73 locus, emphasizing that TP73 is a recurrent target of 1p36 alterations: in a first subclone, it was rearranged with a region on 13q14.2 comprising the DLEU2 locus, while in a second subclone, the partner of TP73 was located on 1p35.1 in a region containing only the ZBTB8A and ZBTB8B loci.


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)

TP73 rearrangements.Schematic representation of the position of BAC probes and loci of interest in patients 050, 008, 141 and 105 (patients with TP73 involvement), adapted from www.ensembl.org. Due to lack of material, the partner locus could not be determined in the case of patient 105. Of note, in patients 050 and 105, given the FISH resolution, we could not rule out an involvement of the WRAP73 locus, which is a member of the WD repeat family, involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation [53].
© Copyright Policy
Related In: Results  -  Collection

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

pone-0026311-g002: TP73 rearrangements.Schematic representation of the position of BAC probes and loci of interest in patients 050, 008, 141 and 105 (patients with TP73 involvement), adapted from www.ensembl.org. Due to lack of material, the partner locus could not be determined in the case of patient 105. Of note, in patients 050 and 105, given the FISH resolution, we could not rule out an involvement of the WRAP73 locus, which is a member of the WD repeat family, involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation [53].
Mentions: No obvious hotspot could be identified except for 2 recurring breakpoints, defined as 2 or more cases harboring the same breakpoint. The first occurred within the TP73 locus, in which two breakpoint patterns were observed (Figure 2): the breakpoint was either between probes RP11-46F15 and RP5-1092A11 in patients 050 and 105, or within the latter probe in patients 008 and 141. In patient 050, the BAC pattern on 9q22.2 suggested an involvement of the CKS2 (a cell cycle regulator [26]), the SECISBP2 or the SEMA4D locus. Due to lack of material, the partner locus of patient 105 could not be identified. In patient 008, the partner locus of TP73 was located in a 3 Mb region on 2q22. Finally, in patient 141, there were 2 balanced translocations, both affecting the TP73 locus, emphasizing that TP73 is a recurrent target of 1p36 alterations: in a first subclone, it was rearranged with a region on 13q14.2 comprising the DLEU2 locus, while in a second subclone, the partner of TP73 was located on 1p35.1 in a region containing only the ZBTB8A and ZBTB8B loci.

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