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

被引:40
作者
Brekke, Helge R.
Ribeiro, Franclim R.
Kolberg, Matthias
Agesen, Trude H.
Lind, Guro E.
Eknaes, Mette
Hall, Kirsten S.
Bjerkehagen, Bodil
van den Berg, Eva
Teixeira, Manuel R.
Mandahl, Nils
Smeland, Sigbjorn
Mertens, Fredrik
Skotheim, Rolf I.
Lothe, Ragnhild A. [1 ]
机构
[1] Oslo Univ Hosp, Rikshosp, Norwegian Radium Hosp, Dept Canc Prevent,Inst Canc Res, NO-0310 Oslo, Norway
关键词
COPY NUMBER CHANGES; SOFT-TISSUE SARCOMA; TOPOISOMERASE-II; ARRAY-CGH; HYBRIDIZATION; NEUROFIBROMATOSIS; GENE; IMBALANCES; EXPRESSION; IDENTIFICATION;
D O I
10.1200/JCO.2009.24.8989
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:1573 / 1582
页数:10
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