Cancer Genome Sequencing


The recent advances in high‐throughput sequencing technologies have enabled several whole cancer genomes to be sequenced. In addition, a number of large‐scale targeted resequencing studies have also been performed previously using Sanger sequencing methods. These studies have identified numerous somatic mutations in cancer genomes and provided new insights into the patterns of mutations in different cancer types. Several challenges remain in cancer genome sequencing such as accurately detecting different types of somatic mutations, the difficulty in identifying driver mutations, bioinformatics and analytical challenges in analysing the sequencing data and the cost of whole genome resequencing restricting the studies to a few genomes. However, cancer genome sequencing will eventually emerge as a routine tool to dissect the cancer genomes especially with the arrival of third generation sequencing technologies. The cancer genome resequencing studies have so far produced encouraging results to stimulate further studies to sequence more cancer genomes. These studies have made a significant contribution to the understanding of the somatic mutational profile of various cancers.

Key Concepts:

  • The genetic alterations of cancer occurring at the DNA sequence level can be classified as germline or somatic.

  • Somatic mutations can occur in the cancer genome in several different forms such as single and double nucleotide variants or base substitutions, small insertion–deletions (indels) and larger structural chromosomal alterations.

  • The recent advances in dissecting the somatic mutational profile of cancer genomes have been driven by high‐throughput or next‐generation sequencing (NGS) technologies which have enabled several whole cancer genomes to be sequenced for the first time.

  • The involvement of somatic mutations in cancer initiation and progression, in addition to germline variations, is well recognised.

  • Cancer genomes are characterised by their genomic instability which results in the occurrence of numerous somatic mutations which has proved challenging to investigate.

  • Although a large number of somatic mutations have been detected in cancer genomes, only a small subset is predicted to be ‘driver’ mutations and the remainder considered ‘passenger’ mutations.

  • Driver mutations are the mutations that initiate and drive oncogenesis steps, such as cell proliferation, tumour growth, angiogenesis, tissue invasion and metastasis.

  • Several challenges remain in cancer genome sequencing such as to accurately detect different types of somatic mutations, the difficulty in identifying driver mutations, bioinformatics and analytical challenges and the cost for whole genome resequencing has restricted the studies to a few genomes.

  • Currently there are no major obstacles in cataloging somatic mutations in cancer genomes. The real challenge lies in data interpretation and how the data can be used to discover new drugs or molecular markers for clinical applications.

  • The ultimate goals of cancer genome sequencing are to improve the clinical management of patients and the creation of personalised medicine through the development of new therapeutic agents which are tailored to the individual based on their genetic information.

Keywords: cancer genome; somatic mutation; driver mutation; whole genome resequencing; next generation sequencing technologies

Figure 1.

Challenges and future directions in cancer genome sequencing.



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Ku, Chee Seng, Naidoo, Nasheen, Hartman, Mikael, and Pawitan, Yudi(Dec 2010) Cancer Genome Sequencing. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0023262]