Pediatric Infratentorial Glioblastomas with Distinct Genotype on FFPE Based aCGH
S Sharma, A Free, Y Mei, SC Peiper, Z Wang, J Cowell. Medical College of Georgia, Augusta, GA; Jefferson Medical College, Philadelphia, PA
Background: Glioblastomas (GBM) are rare in children, but reportedly have more varied outcome and suggested differences in tumor biology as compared to typical GBM of adults. We performed high resolution array Comparative Genomic Hybridization (aCGH) aiming to identify genomic copy number changes that might define pediatric infratentorial glioblastoma.
Design: Three pediatric infratentorial GBM, ages 3.5, 7 and 14 years were identified from pathology records. DNA was extracted from formalin-fixed, paraffin embedded (FFPE) samples, using the WaxFree sample isolation kit (TrimGen), labeled with biotin and hybridized to the Affymetrix 250K Sty 1 Mapping array. Call rate of >75%, for SNPs permitted optimal visualization of chromosome events using Partek Genomics Suite software.
Results: Two tumors occurred in the brainstem and one in spinal cord. While histologically typical, one brainstem tumor showed mainly pleomorphic astrocytic cells, whereas the other brainstem and spinal tumors showed a GFAP positive small cell component. Whole chromosomal gains (#1, # 2) and loss (#20) were seen only in the pleomorphic brainstem GBM, which also showed a high level of segmental genomic copy number changes. Segmental loss involving chromosome 8 was seen in all three tumors (Chr8;133039446-136869494, Chr8;pter-3581577, Chr8;pter-30480019 respectively), whereas loss involving chromosome 16 was seen in only 2 cases with small cell components (Chr16;31827239-qter, Chr16;pter-29754532). Segmental gain of chromosome 7 was shared only between 2 brainstem cases (Chr7;17187166-qter, Chr7;69824947-qter). The spinal GBM showed a relatively stable karyotype with a unique loss of Chr19;32848902-qter. None of the frequent losses, gains and amplifications known to occur in adult GBM were identified.
Conclusions: This FFPE based, high resolution DNA copy number profiling in the examined subset of pediatric infratentorial glioblastomas shows a molecular karyotype that was more characteristic of pediatric embryonal tumors rather than adult GBM.
Tuesday, March 23, 2010 1:15 PM
Platform Session: Section G, Tuesday Afternoon