Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1126-1135 |
| Number of pages | 10 |
| Journal | Genome Research |
| Volume | 28 |
| Issue number | 8 |
| DOIs | |
| State | Published - Aug 1 2018 |
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ASJC Scopus subject areas
- Genetics
- Genetics(clinical)
Cite this
Complex rearrangements and oncogene amplifications revealed by long-read DNA and RNA sequencing of a breast cancer cell line. / 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 Douglas; Hicks, James; Richard McCombie, W.; Schatz, Michael C.
In: Genome Research, Vol. 28, No. 8, 01.08.2018, p. 1126-1135.Research output: Contribution to journal › Article
}
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 -