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

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.

Source: Genome Research - July 13, 2018 Category: Genetics & Stem Cells Authors: Nattestad, M., Goodwin, S., Ng, K., Baslan, T., Sedlazeck, F. J., Rescheneder, P., Garvin, T., Fang, H., Gurtowski, J., Hutton, E., Tseng, E., Chin, C.-S., Beck, T., Sundaravadanam, Y., Kramer, M., Antoniou, E., McPherson, J. D., Hicks, J., McCombie, W. R Tags: RESEARCH Source Type: research