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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 research, 08/2018, Letnik: 28, Številka: 8Journal Article
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.
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