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  • Brekke, Helge R (author)

Genomic Changes in Chromosomes 10, 16, and X in Malignant Peripheral Nerve Sheath Tumors Identify a High-Risk Patient Group.

  • Article/chapterEnglish2010

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  • 2010

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  • LIBRIS-ID:oai:lup.lub.lu.se:52ace0ec-025e-4164-95ce-1ad29c2683ce
  • https://lup.lub.lu.se/record/1552601URI
  • https://doi.org/10.1200/JCO.2009.24.8989DOI

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  • Language:English
  • Summary in:English

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  • Subject category:art swepub-publicationtype
  • Subject category:ref swepub-contenttype

Notes

  • 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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  • Ribeiro, Franclim R (author)
  • Kolberg, Matthias (author)
  • Agesen, Trude H (author)
  • Lind, Guro E (author)
  • Eknæs, Mette (author)
  • Hall, Kirsten S (author)
  • Bjerkehagen, Bodil (author)
  • van den Berg, Eva (author)
  • Teixeira, Manuel R (author)
  • Mandahl, NilsLund University,Lunds universitet,Avdelningen för klinisk genetik,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Clinical Genetics,Department of Laboratory Medicine,Faculty of Medicine(Swepub:lu)kgen-nma (author)
  • Smeland, Sigbjørn (author)
  • Mertens, FredrikLund University,Lunds universitet,Avdelningen för klinisk genetik,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Clinical Genetics,Department of Laboratory Medicine,Faculty of Medicine(Swepub:lu)kgen-fme (author)
  • Skotheim, Rolf I (author)
  • Lothe, Ragnhild A (author)
  • Avdelningen för klinisk genetikInstitutionen för laboratoriemedicin (creator_code:org_t)

Related titles

  • In:Journal of Clinical Oncology28, s. 1573-15821527-7755

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