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Article

Identification of Somatic Structural Variants in Solid Tumors by Optical Genome Mapping

1
Department of Otolaryngology—Head and Neck Surgery, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
2
Department of Biochemistry and Molecular Biology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
3
Bionano Genomics, San Diego, CA 92121, USA
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Silvia Fantozzi
J. Pers. Med. 2021, 11(2), 142; https://doi.org/10.3390/jpm11020142
Received: 22 January 2021 / Revised: 12 February 2021 / Accepted: 15 February 2021 / Published: 18 February 2021
(This article belongs to the Special Issue Recent Developments in Cancer Systems Biology)
Genomic structural variants comprise a significant fraction of somatic mutations driving cancer onset and progression. However, such variants are not readily revealed by standard next-generation sequencing. Optical genome mapping (OGM) surpasses short-read sequencing in detecting large (>500 bp) and complex structural variants (SVs) but requires isolation of ultra-high-molecular-weight DNA from the tissue of interest. We have successfully applied a protocol involving a paramagnetic nanobind disc to a wide range of solid tumors. Using as little as 6.5 mg of input tumor tissue, we show successful extraction of high-molecular-weight genomic DNA that provides a high genomic map rate and effective coverage by optical mapping. We demonstrate the system’s utility in identifying somatic SVs affecting functional and cancer-related genes for each sample. Duplicate/triplicate analysis of select samples shows intra-sample reliability but also intra-sample heterogeneity. We also demonstrate that simply filtering SVs based on a GRCh38 human control database provides high positive and negative predictive values for true somatic variants. Our results indicate that the solid tissue DNA extraction protocol, OGM and SV analysis can be applied to a wide variety of solid tumors to capture SVs across the entire genome with functional importance in cancer prognosis and treatment. View Full-Text
Keywords: optical genome mapping; solid tumors; cancer genomics optical genome mapping; solid tumors; cancer genomics
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MDPI and ACS Style

Goldrich, D.Y.; LaBarge, B.; Chartrand, S.; Zhang, L.; Sadowski, H.B.; Zhang, Y.; Pham, K.; Way, H.; Lai, C.-Y.J.; Pang, A.W.C.; Clifford, B.; Hastie, A.R.; Oldakowski, M.; Goldenberg, D.; Broach, J.R. Identification of Somatic Structural Variants in Solid Tumors by Optical Genome Mapping. J. Pers. Med. 2021, 11, 142. https://doi.org/10.3390/jpm11020142

AMA Style

Goldrich DY, LaBarge B, Chartrand S, Zhang L, Sadowski HB, Zhang Y, Pham K, Way H, Lai C-YJ, Pang AWC, Clifford B, Hastie AR, Oldakowski M, Goldenberg D, Broach JR. Identification of Somatic Structural Variants in Solid Tumors by Optical Genome Mapping. Journal of Personalized Medicine. 2021; 11(2):142. https://doi.org/10.3390/jpm11020142

Chicago/Turabian Style

Goldrich, David Y., Brandon LaBarge, Scott Chartrand, Lijun Zhang, Henry B. Sadowski, Yang Zhang, Khoa Pham, Hannah Way, Chi-Yu J. Lai, Andy W.C. Pang, Benjamin Clifford, Alex R. Hastie, Mark Oldakowski, David Goldenberg, and James R. Broach. 2021. "Identification of Somatic Structural Variants in Solid Tumors by Optical Genome Mapping" Journal of Personalized Medicine 11, no. 2: 142. https://doi.org/10.3390/jpm11020142

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