Cancer gene prioritization for targeted resequencing using FitSNP scores

PloS One
Annelies FieuwKatleen De Preter

Abstract

Although the throughput of next generation sequencing is increasing and at the same time the cost is substantially reduced, for the majority of laboratories whole genome sequencing of large cohorts of cancer samples is still not feasible. In addition, the low number of genomes that are being sequenced is often problematic for the downstream interpretation of the significance of the variants. Targeted resequencing can partially circumvent this problem; by focusing on a limited number of candidate cancer genes to sequence, more samples can be included in the screening, hence resulting in substantial improvement of the statistical power. In this study, a successful strategy for prioritizing candidate genes for targeted resequencing of cancer genomes is presented. Four prioritization strategies were evaluated on six different cancer types: genes were ranked using these strategies, and the positive predictive value (PPV) or mutation rate within the top-ranked genes was compared to the baseline mutation rate in each tumor type. Successful strategies generate gene lists in which the top is enriched for known mutated genes, as evidenced by an increase in PPV. A clear example of such an improvement is seen in colon cancer, where the PPV...Continue Reading

Citations

Apr 1, 1971·Proceedings of the National Academy of Sciences of the United States of America·A G Knudson
Dec 26, 2001·Nucleic Acids Research·Ron EdgarAlex E Lash
Mar 3, 2004·Nature Reviews. Cancer·P Andrew FutrealMichael R Stratton
Oct 12, 2004·Biostatistics·Adam B OlshenMichael Wigler
Sep 9, 2006·Science·Tobias SjöblomVictor E Velculescu
May 15, 2007·Bioinformatics·Sean Davis, Paul S Meltzer
Oct 13, 2007·Science·Laura D WoodBert Vogelstein
Feb 12, 2008·Trends in Genetics : TIG·Elaine R Mardis
Sep 6, 2008·Science·D Williams ParsonsKenneth W Kinzler
Feb 21, 2009·BMC Bioinformatics·Vasyl PihurSomnath Datta
Dec 18, 2010·Science·D Williams ParsonsVictor E Velculescu
Mar 9, 2011·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Nikhil WagleLevi A Garraway

Related Concepts

Gene Dosage
Genome
Pancreatic Carcinoma
Candidate Disease Gene
Neoplasms
Malignant Neoplasm of Pancreas
Malignant Tumor of Colon
Incidence Studies
Gene Mutation
Colorectal Neoplasms

Related Feeds

Cancer Sequencing

Several sequencing approaches are employed to understand and examine tumor development and progression. These include whole genome as well as RNA sequencing. Here is the latest research on cancer sequencing.

Cancer Incidence & Mortality

Cancer has emerged as a global concern due to its increase in incidence and mortality. Efforts are underway to evaluate and develop action plans to reduce the global burden of cancer. Currently, lung cancer, breast cancer and prostate cancer are the leading causes of cancer mortality. Here is the latest research on cancer incidence and mortality.