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Genomic Changes in ...
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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LIBRIS-ID:oai:lup.lub.lu.se:52ace0ec-025e-4164-95ce-1ad29c2683ce
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https://lup.lub.lu.se/record/1552601URI
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https://doi.org/10.1200/JCO.2009.24.8989DOI
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Language:English
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Summary in:English
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Subject category:art swepub-publicationtype
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Subject category:ref swepub-contenttype
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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)
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Kolberg, Matthias
(author)
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Agesen, Trude H
(author)
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Lind, Guro E
(author)
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Eknæs, Mette
(author)
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Hall, Kirsten S
(author)
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Bjerkehagen, Bodil
(author)
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van den Berg, Eva
(author)
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Teixeira, Manuel R
(author)
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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)
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Smeland, Sigbjørn
(author)
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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)
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Skotheim, Rolf I
(author)
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Lothe, Ragnhild A
(author)
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Avdelningen för klinisk genetikInstitutionen för laboratoriemedicin
(creator_code:org_t)
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In:Journal of Clinical Oncology28, s. 1573-15821527-7755
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Brekke, Helge R
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Ribeiro, Francli ...
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Kolberg, Matthia ...
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Agesen, Trude H
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Lind, Guro E
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Eknæs, Mette
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Hall, Kirsten S
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Bjerkehagen, Bod ...
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van den Berg, Ev ...
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Teixeira, Manuel ...
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Mandahl, Nils
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Smeland, Sigbjør ...
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Mertens, Fredrik
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Skotheim, Rolf I
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Lothe, Ragnhild ...
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