203A Universal NGS-Based Oncology Test System
In partnership with pharma companies Illumina is developing a universal NGS- based
oncology test system for multi-analyte companion diagnostics, which will enable
transition from use of single-analyte to panel-based assays for selecting cancer ther-
apies. The new system, which will run assays that detect several variants in parallel,
will be used as part of the partners’ clinical trials of targeted cancer therapies.
Illumina plans to develop, commercialize, and gain regulatory approval for multi-
gene panels for therapy selection, which it previously referred to as Onco Panels.
MiSeqDx, the only NGS-based system that has been FDA-cleared to date, will be
used to develop the universal test system. Illumina’s technology will inform physi-
cians about the molecular make-up of their patients’ tumors, enabling them to match
medicines to the drivers of disease for personalized management.
Analysis of RNA Splicing Events in Cancer
Alternative splicing has a role in several aspects of cancer treatment, including the
failure of the patient to activate the administered drug, high toxicity owing to inap-
propriate metabolism and variability of the apoptotic thresholds necessary to trigger
cell death. Genetic variations within both the patient and the tumor cause changes
in the apoptotic threshold and thus differences in both the toxicity and effi cacy of a
chemotherapy drug. Differential expression of a large number of apoptotic alterna-
tive RNA splice variants has been documented in tumors and shows a correlation
with drug response. An antisense approach can be used to target specifi c anti-
apoptotic splice variants to lower the apoptotic threshold of a tumor cell and there-
fore increase the effi cacy of chemotherapy drugs. As RNA splicing is deregulated in
human cancers, it is likely that such alterations will provide pharmacogenomically
relevant markers. Gene expression profi ling technologies such as DATA (differen-
tial analysis of transcripts with alternative splicing) could be applied to identify
RNA splicing differences between tumor biopsies that respond to treatment com-
pared with those that do not respond.
Analysis of Chromosomal Alterations in Cancer Cells
Cancer cells have a remarkable ability to disable some genes and overuse others,
allowing their unchecked growth into tumors. The most aggressive of these distor-
tions occurs when cells delete or multiply chunks of their own chromosomes. Cells
can simply snip strings of genes from the chromosome, or make many extra copies
of the string and reinsert it into the chromosome. A fast and reliable method can
identify alterations to chromosomes that occur when cells become malignant (Myers
et al. 2004 ). Genomics tools are used to identify thousands of genes at once and
Impact of Molecular Diagnostics on the Management of Cancer