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

Helge R. Brekke, Franclim R. Ribeiro, Matthias Kolberg, Trude H. Ågesen, Guro E. Lind, Mette Eknæs, Kirsten S. Hall, Bodil Bjerkehagen, Eva Van Den Berg, Manuel R. Teixeira, Nils Mandahl, Sigbjørn Smeland, Fredrik Mertens, Rolf I. Skotheim, Ragnhild A. Lothe

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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.

Original languageEnglish (US)
Pages (from-to)1573-1582
Number of pages10
JournalJournal of Clinical Oncology
Volume28
Issue number9
DOIs
StatePublished - Mar 20 2010

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Chromosomes, Human, Pair 16
Chromosomes, Human, Pair 10
Neurilemmoma
DNA Copy Number Variations
Survival
Neurofibromatosis 1
Chromosomes
Genome
Neurofibroma
Comparative Genomic Hybridization
Neoplasms
Multivariate Analysis
RNA
Gene Expression
DNA
Genes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Genomic changes in chromosomes 10, 16, and X in malignant peripheral nerve sheath tumors identify a high-risk patient group. / Brekke, Helge R.; Ribeiro, Franclim R.; Kolberg, Matthias; Ågesen, Trude H.; Lind, Guro E.; Eknæs, Mette; Hall, Kirsten S.; Bjerkehagen, Bodil; Van Den Berg, Eva; Teixeira, Manuel R.; Mandahl, Nils; Smeland, Sigbjørn; Mertens, Fredrik; Skotheim, Rolf I.; Lothe, Ragnhild A.

In: Journal of Clinical Oncology, Vol. 28, No. 9, 20.03.2010, p. 1573-1582.

Research output: Contribution to journalArticle

Brekke, Helge R. ; Ribeiro, Franclim R. ; Kolberg, Matthias ; Ågesen, Trude H. ; Lind, Guro E. ; Eknæs, Mette ; Hall, Kirsten S. ; Bjerkehagen, Bodil ; Van Den Berg, Eva ; Teixeira, Manuel R. ; Mandahl, Nils ; Smeland, Sigbjørn ; Mertens, Fredrik ; Skotheim, Rolf I. ; Lothe, Ragnhild A. / Genomic changes in chromosomes 10, 16, and X in malignant peripheral nerve sheath tumors identify a high-risk patient group. In: Journal of Clinical Oncology. 2010 ; Vol. 28, No. 9. pp. 1573-1582.
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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.",
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T1 - Genomic changes in chromosomes 10, 16, and X in malignant peripheral nerve sheath tumors identify a high-risk patient group

AU - Brekke, Helge R.

AU - Ribeiro, Franclim R.

AU - Kolberg, Matthias

AU - Ågesen, Trude H.

AU - Lind, Guro E.

AU - Eknæs, Mette

AU - Hall, Kirsten S.

AU - Bjerkehagen, Bodil

AU - Van Den Berg, Eva

AU - Teixeira, Manuel R.

AU - Mandahl, Nils

AU - Smeland, Sigbjørn

AU - Mertens, Fredrik

AU - Skotheim, Rolf I.

AU - Lothe, Ragnhild A.

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N2 - 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.

AB - 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.

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