Next-generation sequencing applied to molecular diagnostics

Abstract

Next-generation sequencing technologies have begun to revolutionize the field of cancer genetics through rapid and accurate assessment of a patient’s DNA makeup with minimal cost. These technologies have already led to the realization of the inter- and intra-tumor genetic heterogeneity and the identification of novel mutations and chimeric genes, however, several challenges lie ahead. Given the low number of recurrent somatic genetic aberrations in common types of cancer, the identification of ‘driver’ genetic aberrations has proven challenging. Furthermore, implementation of next-generation sequencing and/or some of its derivatives into routine practice as diagnostic tests will require in-depth understanding of the pitfalls of these technologies and a great degree of bioinformatic expertise. This article focuses on the contribution of next-generation sequencing technologies to diagnosis and cancer prognostication and prediction.

Keywords::

• cancer
• exome
• fusion genes
• genetics
• massively parallel sequencing
• mutations
• third-generation sequencing

Acknowledgements

The authors would like to thank Iwanka Kozarewa for her helpful discussions.

Financial & competing interests disclosure

This work was supported by The Breakthrough Breast Cancer charity. Rachael Natrajan and Jorge S Reis-Filho are funded in part by Breakthrough Breast Cancer. Jorge S Reis-Filho is the recipient of the 2010 CRUK Future Leaders Prize. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.