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Genetic Aberrations Defined by Comparative Genomic Hybridization Distinguish Long-Term from Typical Survivors of Glioblastoma¹

Departments of Laboratory Medicine [B. G. F.] and Neurological Surgery [E. C. B., K. R. L., B. G. F., M. P.], University of California, San Francisco, California 94143; Brain Tumor Center, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030 [K. D. A.]; Department of Medicine, Tom Baker Cancer Center, University of Calgary, Calgary, Alberta, 2N4N2 Canada [J. S., P. F.]; and Department of Laboratory Genetics, Mayo Clinic and Foundation, Rochester, Minnesota 55905 [S. P., R. B. J.]

Glioblastoma (GBM) remains a highly lethal neoplasm, refractory to current therapies. The molecular genetic aberrations most closely related to clinical aggressiveness in GBM have been difficult to identify, perhaps due in part to the short survival range observed in cohorts of GBM patients. To address this, we characterized 39 tumors from rare patients (2–5% of all GBM cases) who experienced long-term survival (>3 years) using comparative genomic hybridization as a genome-wide screen. We then compared the frequency and type of aberrations with those in tumors from 24 typical or short-term survivors [STSs (<1.5 years)]. Losses of 9p and 10 and simple gains of chromosome 7 showed at least trends toward increased frequency in the STS group. Additional aberrations, including loss of 6q and gains of 19q and 20q, were significantly more frequent in the STS group. The presence of 19q loss was exclusive to the long-term survivor (LTS) group. Multivariate analyses indicated that 6q loss, 10q loss, and 19q gain were associated with short-term survival (all P < 0.01). The combination of any two of these three aberrations was seen in 16 of 24 STSs but only 1 of 39 LTSs. This comparison of rare LTSs with STSs (typical GBM survivors) identified 6q loss, 10q loss, and 19q gain, particularly when two or more of these were present, as most closely associated with aggressive clinical behavior in GBM. Loss of 19q may be a marker of long-term survival.

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