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

TitleComplex rearrangements and oncogene amplifications revealed by long-read DNA and RNA sequencing of a breast cancer cell line.
Publication TypeJournal Article
Year of Publication2018
AuthorsNattestad, M, Goodwin, S, Ng, K, Baslan, T, Sedlazeck, FJ, Rescheneder, P, Garvin, T, Fang, H, Gurtowski, J, Hutton, E, Tseng, E, Chin, C-S, Beck, T, Sundaravadanam, Y, Kramer, M, Antoniou, E, McPherson, JD, Hicks, J, W McCombie, R, Schatz, MC
JournalGenome Res
Volume28
Issue8
Pagination1126-1135
Date Published2018 08
ISSN1549-5469
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 oncogene (also known as ), 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.

DOI10.1101/gr.231100.117
Alternate JournalGenome Res.
PubMed ID29954844
PubMed Central IDPMC6071638
Grant ListP30 CA045508 / CA / NCI NIH HHS / United States
R01 HG006677 / HG / NHGRI NIH HHS / United States
T32 GM065094 / GM / NIGMS NIH HHS / United States
UM1 HG008898 / HG / NHGRI NIH HHS / United States