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Gut 62:920-932 doi:10.1136/gutjnl-2011-301935
  • Recent advances in basic science

Next generation sequencing and a new era of medicine

  1. David Duggan2
  1. 1Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
  2. 2The Translational Genomics Research Institute (TGen), Phoenix, Arizona, USA
  1. Correspondence to Dr Graham Casey, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA; gcasey{at}usc.edu
  1. Contributors DC, RH, DD.

Introduction

The 10th anniversary of the publication of the first draft sequence of the human genome was celebrated recently, following the launch of the Human Genome Project in 1990.1 Now, 10 years later, a human genome can be sequenced in less than 10 days and soon will be sequenced routinely within a day. This remarkable progress is due to significant advances in DNA sequencing technologies from Sanger sequencing that has been dominant for nearly 30 years to next generation sequencing (NGS, also termed massively parallel sequencing). The ability to rapidly sequence human genomes and to generate genetic, transcriptomic, epigenetic data and other genome-wide data for a relatively small cost opens up numerous opportunities for translation into the clinic over the next few years. Can the knowledge gained through NGS advances lead to personalized medicine for cancer patients? In this review we provide an overview of NGS technologies and the challenges associated with handling massive amounts of data, data integration, visualization and analysis, followed by a discussion of the biological information that obtained through NGS within the context of colorectal cancer. Finally we will discuss the remaining challenges for NGS to change clinical management of disease.

NGS technologies

The first draft of the human genome was generated using Sanger sequencing (considered first generation sequencing technology), a very successful but labour-intensive approach that required gel electrophoresis to size-separate dideoxy-terminated, PCR amplification products (originally radio-labelled nucleotides were used, but the change to fluorescent dye-labelled nucleotides greatly accelerated the application of this technology). While other sequencing methods existed (such as Maxam–Gilbert sequencing), Sanger sequencing was the mainstay sequencing method used worldwide for nearly 3 decades and has yielded many promising findings in cancer that have already entered the clinic.2 First generation sequencing approaches such as Sanger sequencing relied on sequencing PCR …