Recurrent chromosomal imbalances and structurally abnormal breakpoints within complex karyotypes of malignant peripheral nerve sheath tumour and malignant triton tumour: a cytogenetic and molecular cytogenetic study

Abstract

Background: Cytogenetic studies of malignant peripheral nerve sheath tumours (MPNSTs) and malignant triton tumours (MTTs) are rare. Aims: To undertake cytogenetic analysis of these tumours. Methods: Conventional cytogenetic analysis of 21 MPNSTs and MTTs from 17 patients (nine with peripheral neurofibromatosis (NF1)) was carried out using standard culture and harvesting procedures.For a more precise identification of composite structural rearrangements and marker chromosomes, spectral karyotypic analysis (SKY) was applied to a subset of cases. In addition, EGFR gene copy number was assessed by fluorescence in situ hybridisation (FISH) analysis in a subset of cases. Results: Cytogenetic analysis revealed predominantly complex karyotypes. SKY analysis was useful in further defining many structural anomalies. Structural aberrations most frequently involved chromosomal bands or regions 1p31-36, 4q28-35, 7p22, 11q22-23, 19q13, 20q13, and 22q11-13. Overall, loss of chromosomal material was much more common than gain. Loss of chromosomes or chromosomal regions 1p36 (48%), 3p21-pter (52%), 9p23-pter (57%), 10 (48%), 11q23-qter (48%), 16/16q24 (62%), 17(43%), and 22/22q (48%), and gains of 7/7q (29%) and 8/8q (29%) were most prominent. These gains and losses were distributed equally between MPNST and MTT, demonstrating that these entities are similar with respect to recurrent genomic imbalances. Similarly, none of the recurrent chromosomal breakpoints or imbalances was restricted to either NF1 associated or sporadic MPNSTs. FISH analysis was negative for amplification. Conclusions: These cytogenetic and molecular cytogenetic findings expand the knowledge of chromosomal alterations in MPNST and MTT, and point to possible recurring regions of interest.

Expression profiling of 519 kinase genes in matched malignant peripheral nerve sheath tumor/plexiform neurofibroma samples is discriminatory and identifies mitotic regulators BUB1B, PBK and NEK2 as overexpressed with transformation

“…1,2 Malignant peripheral nerve sheath tumors often show complex karyotypes with losses and gains of chromosome arms as well as focal amplifications and deletions. [3][4][5][6] A number of miRNAs, cell cycle regulators, signaling molecules and transcription factors have been shown to be differentially expressed between neurofibromas and malignant peripheral nerve sheath tumors including CDKN2A, TP53, RB1, EGFR, CD44, PDGFRB, PDGFRA, HGF, MET, IGFR1, SOX9, SOX10, miR-34a and miR-21. 3,[7][8][9][10][11][12][13][14] Neurofibromatosis type 1 patients often have multiple plexiform neurofibromas.…”

Prognostic implication of MET overexpression in myxofibrosarcomas: an integrative array comparative genomic hybridization, real-time quantitative PCR, immunoblotting, and immunohistochemical analysis

“…5 The prospect of genomic profiling with derived targeted therapies is now prompting increasing efforts to characterize cancer genomes. 5 There is mounting evidence that regional gains and/or high-level amplifications on chromosomal arm 7q are recurrently found in various types of bone and soft tissue sarcomas, [6][7][8][9][10][11][12] including myxofibrosarcomas. 8 However, as for myxofibrosarcomas, the pathogenetically relevant target oncogenes on 7q and their prognostic implications remain largely unknown.…”

A cytogenetic analysis in two cases of malignant peripheral nerve sheath tumor showing hypodiploid karyotype

“…The recurrent gains of chromosome 1q, 5p, 6p, 7, 8q, 12, 13q, 15 and 17q the most frequent losses of chromosomes 1p, 9p, 11p, 17p and 17q have been reported (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18). Loss of chromosome 9p is the most common feature in MPNST.…”

“…Their chromosome ploidy distributes between hypodiploid and tetraploid, some tumors have been described as hypodiploid (3)(4)(5)(6)(7)(8). Regardless of ploidy range, however, karyotypes of MPNST exhibit complex abnormalities with numerical and structural changes (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13). Cytogenetic aberrations on chromosomes 1, 2, 5, 7-9, 11-14, 17, 18 and 22 were found to be the most frequent, although no consistent karyotypic patterns have been detected (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18).…”