|Title||Complex rearrangements and oncogene amplifications revealed by long-read DNA and RNA sequencing of a breast cancer cell line.|
|Publication Type||Journal Article|
|Year of Publication||2018|
|Authors||Nattestad, 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|
|Date Published||2018 Jun 28|
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.
|Alternate Journal||Genome Res.|