High-Throughput Functional Validation of Progression Drivers in Lung Adenocarcinoma
Abstract
Cancer cells are endowed with diverse biological capabilities driven by an ensemble of inherited, somatic and epigenetic aberrations. As we enter the era of personalized medicine, characterization of the cancer genome has begun and will continue to influence diagnostic and therapeutic decisions in the clinic. Genome profiling technologies are generating a compendium of genomic aberrations in major cancer lineages with the goal of identifying the most promising therapeutic targets and diagnostic biomarkers. The output from these technologies is radically transforming cancer science. At the same time, these efforts are revealing the complexity of cancer genomes, which are comprised of causal driver aberrations and many more biologically neutral passengers that arise through the unstable nature of tumor genomes. While most cancers acquire one or more well-studied, high frequency driver events (e.g., mutations/gene copy number changes in KRAS, TP53, EGFR, MYC, BRAF, etc.), much less is known about the overly abundant low frequency (<5%) aberrations contributing to tumor progression and response to therapeutics. Comprehensive biological assessment of low frequency aberrations is difficult given their large number and the fact that they may either directly drive tumor progression or indirectly influence tumor behavior through modifying activities of other drivers like KRAS. Moreover, distinguishing driver events from passengers is further complicated by the fact that driver events are shaped by the specific biological context of a given cancer, including its tissue type, microenvironment and other host determinants including the immune system.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2013
- Accession Number
- ADA602932
Entities
People
- Don L Gibbons
Organizations
- The University of Texas MD Anderson Cancer Center