RT Journal
A1 Nattestad, Maria
A1 Goodwin, Sara
A1 Ng, Karen
A1 Baslan, Timour
A1 Sedlazeck, Fritz
A1 Rescheneder, Philipp
A1 Garvin, Tyler
A1 Fang, Han
A1 Gurtowski, James
A1 Hutton, Elizabeth
A1 Tseng, Elizabeth
A1 Chin, Jason
A1 Beck, Timothy
A1 Sundaravadanam, Yogi
A1 Kramer, Melissa
A1 Antoniou, Eric
A1 McPherson, John
A1 Hicks, James
A1 McCombie, W. Richard
A1 Schatz, Michael C
T1 Complex rearrangements and oncogene amplifications revealed by long-read DNA and RNA sequencing of a breast cancer cell line
JF Genome Research 
JO Genome Research 
YR 2018 
FD June 28 
DO 10.1101/gr.231100.117 
SP gr.231100.117 
UL http://genome.cshlp.org/content/early/2018/06/28/gr.231100.117.abstract 
AB 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.