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Complex rearrangements and oncogene amplifications revealed by long-read DNA and RNA sequencing of a breast cancer cell line
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...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory Press
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6071638/ https://www.ncbi.nlm.nih.gov/pubmed/29954844 http://dx.doi.org/10.1101/gr.231100.117 |
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author | Nattestad, Maria Goodwin, Sara Ng, Karen Baslan, Timour Sedlazeck, Fritz J. Rescheneder, Philipp Garvin, Tyler Fang, Han Gurtowski, James Hutton, Elizabeth Tseng, Elizabeth Chin, Chen-Shan Beck, Timothy Sundaravadanam, Yogi Kramer, Melissa Antoniou, Eric McPherson, John D. Hicks, James McCombie, W. Richard Schatz, Michael C. |
author_facet | Nattestad, Maria Goodwin, Sara Ng, Karen Baslan, Timour Sedlazeck, Fritz J. Rescheneder, Philipp Garvin, Tyler Fang, Han Gurtowski, James Hutton, Elizabeth Tseng, Elizabeth Chin, Chen-Shan Beck, Timothy Sundaravadanam, Yogi Kramer, Melissa Antoniou, Eric McPherson, John D. Hicks, James McCombie, W. Richard Schatz, Michael C. |
author_sort | Nattestad, Maria |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6071638 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Cold Spring Harbor Laboratory Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-60716382019-02-01 Complex rearrangements and oncogene amplifications revealed by long-read DNA and RNA sequencing of a breast cancer cell line Nattestad, Maria Goodwin, Sara Ng, Karen Baslan, Timour Sedlazeck, Fritz J. Rescheneder, Philipp Garvin, Tyler Fang, Han Gurtowski, James Hutton, Elizabeth Tseng, Elizabeth Chin, Chen-Shan Beck, Timothy Sundaravadanam, Yogi Kramer, Melissa Antoniou, Eric McPherson, John D. Hicks, James McCombie, W. Richard Schatz, Michael C. Genome Res Research 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. Cold Spring Harbor Laboratory Press 2018-08 /pmc/articles/PMC6071638/ /pubmed/29954844 http://dx.doi.org/10.1101/gr.231100.117 Text en © 2018 Nattestad et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/. |
spellingShingle | Research Nattestad, Maria Goodwin, Sara Ng, Karen Baslan, Timour Sedlazeck, Fritz J. Rescheneder, Philipp Garvin, Tyler Fang, Han Gurtowski, James Hutton, Elizabeth Tseng, Elizabeth Chin, Chen-Shan Beck, Timothy Sundaravadanam, Yogi Kramer, Melissa Antoniou, Eric McPherson, John D. Hicks, James McCombie, W. Richard Schatz, Michael C. Complex rearrangements and oncogene amplifications revealed by long-read DNA and RNA sequencing of a breast cancer cell line |
title | Complex rearrangements and oncogene amplifications revealed by long-read DNA and RNA sequencing of a breast cancer cell line |
title_full | Complex rearrangements and oncogene amplifications revealed by long-read DNA and RNA sequencing of a breast cancer cell line |
title_fullStr | Complex rearrangements and oncogene amplifications revealed by long-read DNA and RNA sequencing of a breast cancer cell line |
title_full_unstemmed | Complex rearrangements and oncogene amplifications revealed by long-read DNA and RNA sequencing of a breast cancer cell line |
title_short | Complex rearrangements and oncogene amplifications revealed by long-read DNA and RNA sequencing of a breast cancer cell line |
title_sort | complex rearrangements and oncogene amplifications revealed by long-read dna and rna sequencing of a breast cancer cell line |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6071638/ https://www.ncbi.nlm.nih.gov/pubmed/29954844 http://dx.doi.org/10.1101/gr.231100.117 |
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