Computational optimisation of targeted DNA sequencing for cancer detection release_cntcfyvh45avzk3bc7mgg264w4

by Pierre Martinez, Nicholas McGranahan, Nicolai Juul Birkbak, Marco Gerlinger, Charles Swanton

Published in Scientific Reports by Springer Nature.

2013   Volume 3, p3309

Abstract

Despite recent progress thanks to next-generation sequencing technologies, personalised cancer medicine is still hampered by intra-tumour heterogeneity and drug resistance. As most patients with advanced metastatic disease face poor survival, there is need to improve early diagnosis. Analysing circulating tumour DNA (ctDNA) might represent a non-invasive method to detect mutations in patients, facilitating early detection. In this article, we define reduced gene panels from publicly available datasets as a first step to assess and optimise the potential of targeted ctDNA scans for early tumour detection. Dividing 4,467 samples into one discovery and two independent validation cohorts, we show that up to 76% of 10 cancer types harbour at least one mutation in a panel of only 25 genes, with high sensitivity across most tumour types. Our analyses demonstrate that targeting "hotspot" regions would introduce biases towards in-frame mutations and would compromise the reproducibility of tumour detection.
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Type  article-journal
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Date   2013-12-03
Language   en ?
DOI  10.1038/srep03309
PubMed  24296834
PMC  PMC6506443
Wikidata  Q53080459
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