Existing and emerging technologies for tumor genomic profiling

Abstract

Ongoing global genome characterization efforts are revolutionizing our knowledge of cancer genomics and tumor biology. In parallel, information gleaned from these studies on driver cancer gene alterations--mutations, copy number alterations, translocations, and/or chromosomal rearrangements--an be leveraged, in principle, to develop a cohesive framework for individualized cancer treatment. These possibilities have been enabled, to a large degree, by revolutionary advances in genomic technologies that facilitate systematic profiling for hallmark cancer genetic alterations at increasingly fine resolutions. Ongoing innovations in existing genomics technologies, as well as the many emerging technologies, will likely continue to advance translational cancer genomics and precision cancer medicine.

Fig 1.

Categories of genomic alterations and technologies for detection. Many of the hallmark alterations in cancer are currently detected by using a multitude of existing technologies, often in a serial fashion, each using an appreciable amount of nucleic acid. Newer sequencing-based methodologies are capable of interrogating many types of cancer alterations in one composite, sensitive test. CGH, comparative genomic hybridization; ChIP-Seq, chromatin immunoprecipitation followed by massively parallel sequencing; FISH, fluorescent in situ hybridization; IHC, immunohistochemistry; PCR, polymerase chain reaction; RNA-Seq, RNA sequencing, also known as transcriptome sequencing; SNP, single nucleotide polymorphism; Targ-Seq, targeted sequencing; WES, whole-exome sequencing; WGS, whole-genome sequencing.

Fig 2.

The decrease in cost of genome sequencing facilitated by massively parallel sequencing technologies. The cost of sequencing has decreased at a rate faster than Moore's law in the past 10 years. The data from 2001 through 2007 represent the costs of generating DNA sequences by using Sanger-based chemistries and capillary-based instruments (first-generation sequencing platforms). Starting in 2008, the data represent the costs of generating DNA sequences by using second-generation sequencing technologies. The change in instruments represents the rapid evolution of DNA sequencing technologies that has occurred in recent years. Landmark events are also indicated on the timeline. The release of various second- and third-generation technologies is indicated in blue boxes. IHGSC, International Human Genome Sequencing Consortium. Data adapted from the National Human Genome Research Institute Web site.

Fig 3.

Existing and emerging sequencing technologies. Comparison of the generations of sequencing technologies, illustrating the similarities and differences in methodologies and some sequencing characteristics. PCR, polymerase chain reaction.