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Open Access Highly Accessed Research article

Discovery of structural alterations in solid tumor oligodendroglioma by single molecule analysis

Mohana Ray1, Steve Goldstein1, Shiguo Zhou1, Konstantinos Potamousis1, Deepayan Sarkar2, Michael A Newton34, Elizabeth Esterberg3, Christina Kendziorski3, Oliver Bogler5 and David C Schwartz1*

Author Affiliations

1 Laboratory for Molecular and Computational Genomics, Department of Chemistry, Laboratory of Genetics, UW Biotechnology Center, University of Wisconsin-Madison, Madison, WI 53706, USA

2 Theoretical Statistics and Mathematics Unit, Indian Statistical Institute, Delhi, India

3 Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, WI 53706, USA

4 Department of Statistics, University of Wisconsin-Madison, Madison, WI 53706, USA

5 M.D. Anderson Cancer Center, University of Texas, Houston, TX 77030, USA

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BMC Genomics 2013, 14:505  doi:10.1186/1471-2164-14-505

Published: 26 July 2013

Abstract

Background

Solid tumors present a panoply of genomic alterations, from single base changes to the gain or loss of entire chromosomes. Although aberrations at the two extremes of this spectrum are readily defined, comprehensive discernment of the complex and disperse mutational spectrum of cancer genomes remains a significant challenge for current genome analysis platforms. In this context, high throughput, single molecule platforms like Optical Mapping offer a unique perspective.

Results

Using measurements from large ensembles of individual DNA molecules, we have discovered genomic structural alterations in the solid tumor oligodendroglioma. Over a thousand structural variants were identified in each tumor sample, without any prior hypotheses, and often in genomic regions deemed intractable by other technologies. These findings were then validated by comprehensive comparisons to variants reported in external and internal databases, and by selected experimental corroborations. Alterations range in size from under 5 kb to hundreds of kilobases, and comprise insertions, deletions, inversions and compound events. Candidate mutations were scored at sub-genic resolution and unambiguously reveal structural details at aberrant loci.

Conclusions

The Optical Mapping system provides a rich description of the complex genomes of solid tumors, including sequence level aberrations, structural alterations and copy number variants that power generation of functional hypotheses for oligodendroglioma genetics.

Keywords:
Cancer genomics; Oligodendroglioma; Single molecule; Optical mapping; Structural variation; Mutation