Nattestad, M., Goodwin, S., Ng, K., Baslan, T., Sedlazeck, F., Rescheneder, P., Garvin, T., Fang, H., Gurtowski, J., Hutton, E., Tseng, E., Chin, J., Beck, T., Sundaravadanam, Y., Kramer, M., Antoniou, E., McPherson, J., Hicks, J., McCombie, W. R., Schatz, M. C. (August 2018) Complex rearrangements and oncogene amplifications revealed by long-read DNA and RNA sequencing of a breast cancer cell line. Genome Res, 28 (8). pp. 1126-1135. ISSN 1088-9051
Abstract
The SK-BR-3 cell line is one of the most important models for HER2+ breast cancers, which affect one in five breast cancer patients. SK-BR-3 is known to be highly rearranged although much of the variation is in complex and repetitive regions that may be underreported. Addressing this, we sequenced SK-BR-3 using long-read single molecule sequencing from Pacific Biosciences, and develop one of the most detailed maps of structural variations (SVs) in a cancer genome available with nearly 20,000 variants present, most of which were missed by short read sequencing. Surrounding the important ERBB2 oncogene (also known as HER2), we discover a complex sequence of nested duplications and translocations, suggesting a punctuated progression. Full-length transcriptome sequencing further revealed several novel gene fusions within the nested genomic variants. Combining long-read genome and transcriptome sequencing enables an in-depth analysis of how SVs disrupt the genome and sheds new light on the complex mechanisms involved in cancer genome evolution.
| Item Type: | Paper |
|---|---|
| Subjects: | diseases & disorders > cancer > cancer types > breast cancer bioinformatics > genomics and proteomics > genetics & nucleic acid processing > transcriptomes Investigative techniques and equipment > assays > whole genome sequencing |
| CSHL Authors: | |
| Communities: | CSHL labs > Hicks lab CSHL labs > McCombie lab CSHL labs > Schatz lab School of Biological Sciences > Publications CSHL Cancer Center Program > Cancer Genetics and Genomics Program |
| Depositing User: | Matthew Dunn |
| Date: | August 2018 |
| Date Deposited: | 15 Aug 2018 15:48 |
| Last Modified: | 05 Nov 2020 14:53 |
| PMCID: | PMC6071638 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/37109 |
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