Observations of the genomic landscape beyond 1p19q deletions and EGFR amplification in glioma

Abstract

Background: With recent advancements in molecular techniques, the opportunities to gather whole genome information have increased, even in degraded samples such as FFPE tissues. As a result, a broader view of the genomic landscape of solid tumors may be explored. Whole genome copy number and loss of heterozygosity patterns can advance our understanding of mechanisms and complexity of various tumors.

Results: Genome-wide alterations involving copy number changes and loss of heterozygosity were identified in 17 glioma samples with positive FISH results for 1p19q co-deletions (n = 9) or EGFR amplification (n = 8). Gliomas positive for 1p19q co-deletions did not have other frequently recurrent genomic alterations. Additional copy-number alterations were observed in individual cases, and consisted primarily of large-scale changes, including gains or losses of entire chromosomes. The genomic architecture of EGFR amplified gliomas was much more complex, with a high number of gains and losses across the genome. Recurrent alterations in EGFR amplified gliomas were both focal, such as CDKN2A homozygous deletions, and large, such as chromosome 10 loss.

Conclusions: Microarray enabled a broader picture of the genomic alterations occurring in glioma cases. Gliomas with 1p19q co-deletion had a relatively quiet genome, apart from the selected co-deletion. Additional alterations in isolated cases, involved primarily larger aberrations. On the other hand, EGFR amplified cases tended to be more complex and have specific abnormalities associated with the EGFR amplification. Furthermore, 1p19q co-deletions and EGFR amplification associated copy number changes appeared to often be mutually exclusive.

Keywords: Copy number change; FFPE array; Genomic landscape; Glioma; Microarray; OncoScan.

Fig. 1

1p19q co-deletion cohort. a Highlights the 1p and 19q co-deletions (deletions marked by indicated region). Case 1p19q-03 had two copies of 1p and 19q, but was tetraploid throughout the remainder of the genome (blue arrow). b Highlights whole chromosomal changes observed in this cohort including gains (blue arrows) and deletions (red arrows)

Fig. 2

Copy number changes observed in GBMs. a A representative sample of EGFR amplification that was confirmed by array in each case (blue circle). b Additional CNCs observed across the GBM cohort

Fig. 3

Additional copy number changes observed in the GBM cohort. a Whole genome overview of the glioblastoma cohort includes b Chromosome 7 complexity, c CDKN2A/B deletions and d Chromosome 10 deletions