Intratumoral heterogeneity in human solid tumors represents a major barrier for the development of effective molecular treatment strategies, since treatment efficacies will reflect the molecular variegation in individual tumors. In glioblastoma, the generation of composite genomic profiles from bulk tumor samples has allowed one to map the genomic amplifications of putative genetic drivers and to prioritize therapeutic targeting strategies aimed at eradicating the tumor burden. Notably, amplification of multiple receptor tyrosine kinases (RTKs) within a single tumor specimen obtained from patients is frequently observed. In this study, use of a detailed multi-colour FISH mapping procedure in pathological specimens revealed a mutual exclusivity of gene amplification in the majority of glioblastoma tumors examined. In particular, the two most commonly amplified RTK genes, EGFR and PDGFRA, were found to be present in variable proportions across the tumors, with one or the other gene predominating in certain areas of the same specimen. Our findings have profound implications for designing efficacious therapeutic regimens, since it remains unclear how the cells with different gene amplification events contribute to disease propagation or the response to molecular targeted therapies.

PMID: 22311673 [PubMed - as supplied by publisher] Source: National Library of Medicine.