Complex rearrangements and oncogene amplifications revealed by long-read DNA and RNA sequencing of a breast cancer cell line

Maria Nattestad, Sara Goodwin, Karen Ng, Timour Baslan, Fritz J. Sedlazeck, Philipp Rescheneder, Tyler Garvin, Han Fang, James Gurtowski, Elizabeth Hutton, Elizabeth Tseng, Chen Shan Chin, Timothy Beck, Yogi Sundaravadanam, Melissa Kramer, Eric Antoniou, John Douglas Mcpherson, James Hicks, W. Richard McCombie, Michael C. Schatz

Research output: Contribution to journalArticle

21 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1126-1135
Number of pages10
JournalGenome Research
Volume28
Issue number8
DOIs
StatePublished - Aug 1 2018

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RNA Sequence Analysis
DNA Sequence Analysis
Oncogenes
Genome
Breast Neoplasms
Transcriptome
Cell Line
Genomic Structural Variation
Nucleic Acid Repetitive Sequences
Gene Fusion
Neoplasms

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Nattestad, M., Goodwin, S., Ng, K., Baslan, T., Sedlazeck, F. J., Rescheneder, P., ... Schatz, M. C. (2018). Complex rearrangements and oncogene amplifications revealed by long-read DNA and RNA sequencing of a breast cancer cell line. Genome Research, 28(8), 1126-1135. https://doi.org/10.1101/gr.231100.117

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 Douglas; Hicks, James; Richard McCombie, W.; Schatz, Michael C.

In: Genome Research, Vol. 28, No. 8, 01.08.2018, p. 1126-1135.

Research output: Contribution to journalArticle

Nattestad, M, Goodwin, S, Ng, K, Baslan, T, Sedlazeck, FJ, Rescheneder, P, Garvin, T, Fang, H, Gurtowski, J, Hutton, E, Tseng, E, Chin, CS, Beck, T, Sundaravadanam, Y, Kramer, M, Antoniou, E, Mcpherson, JD, Hicks, J, Richard McCombie, W & Schatz, MC 2018, 'Complex rearrangements and oncogene amplifications revealed by long-read DNA and RNA sequencing of a breast cancer cell line', Genome Research, vol. 28, no. 8, pp. 1126-1135. https://doi.org/10.1101/gr.231100.117
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 Douglas ; Hicks, James ; Richard McCombie, W. ; Schatz, Michael C. / Complex rearrangements and oncogene amplifications revealed by long-read DNA and RNA sequencing of a breast cancer cell line. In: Genome Research. 2018 ; Vol. 28, No. 8. pp. 1126-1135.
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