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

BMC Genomics

Research Article

Christina Kendziorski¹  Elizabeth Esterberg¹  Michael A Newton²  Mohana Ray³  Shiguo Zhou³  Steve Goldstein³  David C Schwartz³  Konstantinos Potamousis³  Oliver Bogler⁴  Deepayan Sarkar⁵ 

[1] Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, 53706, Madison, WI, USA;Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, 53706, Madison, WI, USA;Department of Statistics, University of Wisconsin-Madison, 53706, Madison, WI, USA;Laboratory for Molecular and Computational Genomics, Department of Chemistry, Laboratory of Genetics, UW Biotechnology Center, University of Wisconsin-Madison, 53706, Madison, WI, USA;M.D. Anderson Cancer Center, University of Texas, 77030, Houston, TX, USA;Theoretical Statistics and Mathematics Unit, Indian Statistical Institute, Delhi, India;

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

DOI  :  10.1186/1471-2164-14-505

 received in 2013-03-07, accepted in 2013-07-23,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundSolid 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.ResultsUsing 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.ConclusionsThe 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.

【 授权许可】

Unknown   
© Ray et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.