The Role of New Sequencing Technology in Identifying Rare Mutations in New Susceptibility Genes for Cancer

Abstract

Massively parallel sequencing (MPS) has transformed our capacity to analyze the genome. Technology now facilitates the production of hundreds of gigabases of sequencing data from single instrument runs and is flexible to study design, allowing analyses of full genomes through a range of targeted sequencing strategies involving one to thousands of samples. The search for new cancer susceptibility genes is no longer limited by sequencing technology; theoretically, MPS can be advantageous to studies searching for genetic variation responsible for cancer predisposition across the risk spectrum. Genetically uncharacterized rare syndromes are now being unraveled at a much increased rate (including rare cancer-related syndromes), yet complex diseases such as common cancers have proven to be more challenging. MPS has revealed the complexity of the human genome, and our current study designs and bioinformatic and computational approaches need to be refined to realize the full potential of MPS for it contribute to the identification of new cancer susceptibility genes.

Annokey: an annotation tool based on key term search of the NCBI Entrez Gene database

“…The detection of rare variant associations with disease is one of many applications enabled by this new technology [2]. However, current analysis pipelines tend to produce large numbers of genetic variants, only a small subset of which are likely to be relevant to the phenotype under study [3,4].…”

“…Recent advances in high-throughput DNA sequencing have allowed large regions of a sample genome (or genomes) to be sequenced rapidly at high coverage [ 1 ]. The detection of rare variant associations with disease is one of many applications enabled by this new technology [ 2 ]. However, current analysis pipelines tend to produce large numbers of genetic variants, only a small subset of which are likely to be relevant to the phenotype under study [ 3 , 4 ].…”