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

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...

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Detalles Bibliográficos
Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6071638/
https://www.ncbi.nlm.nih.gov/pubmed/29954844
http://dx.doi.org/10.1101/gr.231100.117
Descripción
Sumario: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.