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

被引：118

作者：

Nattestad, Maria ^{[1
]}

Goodwin, Sara ^{[1
]}

Ng, Karen ^{[2
]}

Baslan, Timour ^{[3
]}

Sedlazeck, Fritz J. ^{[4
,5
]}

Rescheneder, Philipp ^{[6
]}

Garvin, Tyler ^{[1
]}

Fang, Han ^{[1
]}

Gurtowski, James ^{[1
]}

Hutton, Elizabeth ^{[1
]}

Tseng, Elizabeth ^{[7
]}

Chin, Chen-Shan ^{[7
]}

Beck, Timothy ^{[2
]}

Sundaravadanam, Yogi ^{[2
]}

Kramer, Melissa ^{[1
]}

Antoniou, Eric ^{[1
]}

McPherson, John D. ^{[8
]}

Hicks, James ^{[1
]}

McCombie, W. Richard ^{[1
]}

Schatz, Michael C. ^{[1
,4
]}

机构：

[1] Cold Spring Harbor Lab, POB 100, Cold Spring Harbor, NY 11724 USA

[2] Ontario Inst Canc Res, Toronto, ON M5G 0A3, Canada

[3] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA

[4] Johns Hopkins Univ, Baltimore, MD 21211 USA

[5] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA

[6] Med Univ Vienna, Univ Vienna, Ctr Integrat Bioinformat Vienna, Max F Perutz Labs, A-1030 Vienna, Austria

[7] Pacific Biosci, Menlo Pk, CA 94025 USA

[8] UC Davis Comprehens Canc Ctr, Sacramento, CA 95817 USA

来源：

GENOME RESEARCH | 2018年 / 28卷 / 08期

基金：

美国国家卫生研究院; 美国国家科学基金会;

关键词：

HUMAN GENOME; STRUCTURAL VARIATIONS; PAIRED-END; MUTATIONS; NUMBER; DISCOVERY; VARIANTS; GERMLINE; PATTERNS; GMAP;

D O I：

10.1101/gr.231100.117

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：1126 / 1135

页数：10

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