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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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2018
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.
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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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