PT  - JOURNAL ARTICLE
AU  - Maria Nattestad
AU  - Sara Goodwin
AU  - Karen Ng
AU  - Timour Baslan
AU  - Fritz J. Sedlazeck
AU  - Philipp Rescheneder
AU  - Tyler Garvin
AU  - Han Fang
AU  - James Gurtowski
AU  - Elizabeth Hutton
AU  - Elizabeth Tseng
AU  - Chen-Shan Chin
AU  - Timothy Beck
AU  - Yogi Sundaravadanam
AU  - Melissa Kramer
AU  - Eric Antoniou
AU  - John D. McPherson
AU  - James Hicks
AU  - W. Richard McCombie
AU  - Michael C. Schatz
TI  - Complex rearrangements and oncogene amplifications revealed by long-read DNA and RNA sequencing of a breast cancer cell line
AID  - 10.1101/174938
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 174938
4099  - http://biorxiv.org/content/early/2017/08/10/174938.short
4100  - http://biorxiv.org/content/early/2017/08/10/174938.full
AB  - 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 prior efforts. Surrounding the important HER2 locus, 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 transcriptome and sheds new light on the complexity of cancer progression.