TY - JOUR
T1 - Complex rearrangements and oncogene amplifications revealed by long-read DNA and RNA sequencing of a breast cancer cell line
AU - Nattestad, Maria
AU - Goodwin, Sara
AU - Ng, Karen
AU - Baslan, Timour
AU - Sedlazeck, Fritz J.
AU - Rescheneder, Philipp
AU - Garvin, Tyler
AU - Fang, Han
AU - Gurtowski, James
AU - Hutton, Elizabeth
AU - Tseng, Elizabeth
AU - Chin, Chen Shan
AU - Beck, Timothy
AU - Sundaravadanam, Yogi
AU - Kramer, Melissa
AU - Antoniou, Eric
AU - Mcpherson, John Douglas
AU - Hicks, James
AU - Richard McCombie, W.
AU - Schatz, Michael C.
PY - 2018/8/1
Y1 - 2018/8/1
N2 - 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.
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.
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U2 - 10.1101/gr.231100.117
DO - 10.1101/gr.231100.117
M3 - Article
C2 - 29954844
AN - SCOPUS:85050861770
VL - 28
SP - 1126
EP - 1135
JO - Genome Research
JF - Genome Research
SN - 1088-9051
IS - 8
ER -