Chromosome 9q and 16q loss identified by genome-wide pooled-analysis are associated with tumor aggressiveness in patients with classic medulloblastoma |
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Authors: | Coco Simona Valdora Francesca Bonassi Stefano Scaruffi Paola Stigliani Sara Oberthuer André Berthold Frank Andolfo Immacolata Servidei Tiziana Riccardi Riccardo Basso Eleonora Iolascon Achille Tonini Gian Paolo |
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Institution: | Translational Oncopathology, National Cancer Research Institute (IST), Genoa, Italy. |
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Abstract: | Medulloblastoma (MB) is one of the most aggressive pediatric brain tumor. We report genome-wide pooled-analysis of classic MB variant of patients over 3 years of age at diagnosis. We combined array comparative genomic hybridization (aCGH) results from experimental analysis (31 cases) with two public databases (55 cases) in a final evaluation of 86 MBs. The most common chromosome structural aberrations were gains of 17q (45.3%), 1q (22.1%), and losses of 8p (15.1%), 10q (19.8%), 17p (37.2%), and 16q (16.3%). Isochromome (17q) was observed in 29.1% MBs. A significant association between poor patients survival and losses of 9q (p?0.0023), 10q (p?0.012), and 16q (p?0.036) was observed. Univariate analysis showed association of 9q loss (p?0.008) and 16q loss (p?=?0.05) with adverse overall survival (OS). Chromosome 6 monosomy was a protective event although statistically borderline (p?=?0.066). After adjusting for confounding factors, a poor OS was found for patients whose tumor has 9q loss hazard ratio (HR)?=?3.97; p?0.006) or 16q loss (HR?=?2.41; p?=?0.038). Our results highlight the importance of genomic studies in different MB histological variants and indicate a genotype-phenotype correlation. |
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