Genomic imbalances of 7p and 17q in malignant peripheral nerve sheath tumors are clinically relevant

Abstract

We investigated 31 malignant peripheral nerve sheath tumors (MPNSTs) from 23 patients by means of comparative genomic hybridization (CGH) in order to study quantitative genomic aberrations of these tumors. Twenty‐one of the 23 patients revealed changes, with a mean value of 11 aberrations per sample (range 2–29). The minimal common regions of the most frequent gains were 8q23‐q24.1 (12 cases), 5p14 (11 cases), and 6p22‐pter, 7p15‐p21, 7q32‐q35, 8q21.1‐q22, 8q24.2‐qter, and 17q22‐qter (10 cases each). Seventeen high‐level amplifications were detected in eight of the 21 samples. In three cases, the high‐level amplifications involved 8q24.1‐qter, and in two cases each the high‐level amplifications involved regions 5p14, 7p14‐pter, 8q21.1‐q23, and 13q32‐q33. The minimal common region of frequent losses was 14q24.3‐qter (five cases). The gain of 8q as a single common change in the primary tumor, the recurrence, and the metastasis from the same patient suggests that this aberration is an early change in the tumorigenesis of MPNSTs. Comparable aberrations were observed in separate tumors of the same patients affected by Recklinghausen's disease, indicating a limited number of accidental secondary changes. In sporadic MPNSTs, the most frequent gains were narrowed down predominantly to 5p, 6, 8q, and 20q, whereas in MPNSTs from patients with Recklinghausen's disease, there was most often a gain in 7q, 8q, 15q, and 17q. The occurrence of gain of both 7p15‐p21 and 17q22‐qter was associated with a statistically significant poor overall survival rate (P = 0.0096). Genes Chromosomes Cancer 25:205–211, 1999. © 1999 Wiley‐Liss, Inc.

Distinct chromosomal imbalances in pleomorphic and in high‐grade dedifferentiated liposarcomas

“…Moreover, in 2 pleomorphic and in 4 dedifferentiated LS high level amplifications were detected within this subregion that harbors with MYB at 6q23.3-q24 a potential candidate oncogene. Frequent gains of 6q23-q24 including some amplicons were also identified in leiomyosarcomas 27,28 and malignant peripheral nerve sheath tumors 29,30 while being generally absent in well-differentiated LS/ALT. [23][24][25][26] Overrepresentations of chromosomal subregion 12q24 were likewise detected in about half of both the pleomorphic and the dedifferentiated LS.…”

“…[23][24][25][26] Overrepresentations of chromosomal subregion 12q24 were likewise detected in about half of both the pleomorphic and the dedifferentiated LS. Gains of 12q24 have also been observed frequently in malignant peripheral nerve sheath tumors 29,30 while being mostly absent in well-differentiated LS/ALT. [23][24][25][26] Therefore, overrepresentations of 12q24 seem to be associated with tumor progression in lipogenic sarcomas.…”

“…Recurrent overrepresentations and amplifications of this subregion or part of it have also been described in other aggressive sarcomas such as osteosarcomas, MFH, malignant peripheral nerve sheath tumors and leiomyosarcomas with increasing size. 14,27,29,30 In gastrointestinal stromal tumors gains in 5p13-p15 were associated with malignancy and tumor progression. 31 Because the well-differentiated LS/ALT examined by CGH in the literature [23][24][25][26] and the great majority of dedifferentiated LS analyzed in our study were devoid of any detectable 5p aberrations, gains and amplicons of 5p13-p15 seem to be associated with increasing malignancy in lipogenic sarcomas as well.…”

Gains of 13q are correlated with a poor prognosis in liposarcoma

“…15 Chromosomal regions with a green to red ratio above 1.25 were considered to be overrepresented (gains), whereas regions with a ratio below 0.75 were considered to be under-represented (losses). The cutoff value for high-level amplifications was 1.5 according to Kallioniemi et al 14 The results were confirmed by calculating the double standard deviation of the individual ratio profiles for each chromosome within the same experiment.…”

“…CGH was performed as described by Kallioniemi et al 14 but with some previously reported modifications. 15 Briefly, tumor DNA was labeled with biotin-16-dUTP, and reference DNA was labeled with digoxigenin-11-dUTP (Boehringer Mannheim, Mannheim, Germany) by using nick translation. Hybridization was performed for 3 days at 371C.…”