Genomic changes in chromosomes 10, 16, and X in malignant peripheral nerve sheath tumors identify a high-risk patient group

J Clin Oncol. 2010 Mar 20;28(9):1573-82. doi: 10.1200/JCO.2009.24.8989. Epub 2010 Feb 16.

Abstract

Purpose: The purpose of this study was to identify genetic aberrations contributing to clinical aggressiveness of malignant peripheral nerve sheath tumors (MPNSTs).

Patients and methods: Samples from 48 MPNSTs and 10 neurofibromas were collected from 51 patients with (n = 31) or without (n = 20) neurofibromatosis type 1 (NF1). Genome-wide DNA copy number changes were assessed by chromosomal and array-based comparative genomic hybridization (CGH) and examined for prognostic significance. For a subset of 20 samples, RNA microarray data were integrated with the genome data to identify potential target genes.

Results: Forty-four (92%) MPNSTs displayed DNA copy number changes (median, 18 changes per tumor; range, 2 to 35 changes). Known frequent chromosomal gains at chromosome arms 8q (69%), 17q (67%), and 7p (52%) and losses from 9p (50%), 11q (48%), and 17p (44%) were confirmed. Additionally, gains at 16p or losses from 10q or Xq identified a high-risk group with only 11% 10-year disease-specific survival (P = .00005). Multivariate analyses including NF1 status, tumor location, size, grade, sex, complete remission, and initial metastatic status showed that the genomic high-risk group was the most significant predictor of poor survival. Several genes whose expression was affected by the DNA copy number aberrations were identified.

Conclusion: The presence of specific genetic aberrations was strongly associated with poor survival independent of known clinical risk factors. Conversely, within the total patient cohort with 34% 10-year disease-specific survival, a low-risk group was identified: without changes at chromosomes 10q, 16p, or Xq in their MPNSTs, the patients had 74% 10-year survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Chromosomes, Human, Pair 10 / genetics*
  • Chromosomes, Human, Pair 16 / genetics*
  • Chromosomes, Human, X / genetics*
  • DNA Copy Number Variations*
  • Female
  • Gene Expression
  • Genome
  • Humans
  • Male
  • Middle Aged
  • Nerve Sheath Neoplasms / genetics*
  • Nerve Sheath Neoplasms / mortality
  • Nervous System Neoplasms / genetics*
  • Nervous System Neoplasms / mortality
  • Neurofibromatosis 1 / genetics
  • Prognosis
  • Risk Factors
  • Survival Analysis
  • Young Adult