Omics-based studies have recently revealed phenomena with fundamental implications for the development of next generation diagnostics by genome-wide sequencing and gene expression profiling and for molecularly guided treatment strategies.
In contrast to current routine histological and molecular marker diagnosis, the heterogeneity of distinct molecular patterns of different regions of a tumor have to be considered. Omics-based studies demonstrate that molecular profiles, which till very recently were considered distinct subtypes of gliomas, were now demonstrated in different regions within the same tumor.
These studies also demonstrate that patient and tumor specific genomic and transcription profiles are dynamic and evolve during tumor progression and recurrence. This “molecular drift” is not simply time dependent or random, but influenced by the treatment modality. For example, the alkylating agent temozolomide induces genetic alterations including impairment of the DNA mismatch repair gene complex. As a consequence this leads to secondary methylation resistance and resistance against alkylating agents.
This strongly argues that molecular profiling of a single biopsy at time of first diagnosis of a glioblastoma and prior to treatment will not be predictive of strategies effective when tumors recur after first line radiation-chemotherapy.