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

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.