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

共 53 条

[1]

[Anonymous], ALIGNING SEQUENCE RE, DOI DOI 10.48550/ARXIV.1303.3997

[2]

Arthur JG, 2018, BIORXIV, DOI [10.1101/200170, DOI 10.1101/200170]

[3] A novel bioinformatics pipeline for identification and characterization of fusion transcripts in breast cancer and normal cell lines [J].

Asmann, Yan W. ;

Hossain, Asif ;

Necela, Brian M. ;

Middha, Sumit ;

Kalari, Krishna R. ;

Sun, Zhifu ;

Chai, High-Seng ;

Williamson, David W. ;

Radisky, Derek ;

Schroth, Gary P. ;

Kocher, Jean-Pierre A. ;

Perez, Edith A. ;

Thompson, E. Aubrey .

NUCLEIC ACIDS RESEARCH, 2011, 39 (15) :e100

[4] Resolving the complexity of the human genome using single-molecule sequencing [J].

Chaisson, Mark J. P. ;

Huddleston, John ;

Dennis, Megan Y. ;

Sudmant, Peter H. ;

Malig, Maika ;

Hormozdiari, Fereydoun ;

Antonacci, Francesca ;

Surti, Urvashi ;

Sandstrom, Richard ;

Boitano, Matthew ;

Landolin, Jane M. ;

Stamatoyannopoulos, John A. ;

Hunkapiller, Michael W. ;

Korlach, Jonas ;

Eichler, Evan E. .

NATURE, 2015, 517 (7536) :608-U163

[5] BreakTrans: uncovering the genomic architecture of gene fusions [J].

Chen, Ken ;

Navin, Nicholas E. ;

Wang, Yong ;

Schmidt, Heather K. ;

Wallis, John W. ;

Niu, Beifang ;

Fan, Xian ;

Zhao, Hao ;

McLellan, Michael D. ;

Hoadley, Katherine A. ;

Mardis, Elaine R. ;

Ley, Timothy J. ;

Perou, Charles M. ;

Wilson, Richard K. ;

Ding, Li .

GENOME BIOLOGY, 2013, 14 (08)

[6] Manta: rapid detection of structural variants and indels for germline and cancer sequencing applications [J].

Chen, Xiaoyu ;

Schulz-Trieglaff, Ole ;

Shaw, Richard ;

Barnes, Bret ;

Schlesinger, Felix ;

Kallberg, Morten ;

Cox, Anthony J. ;

Kruglyakl, Semyon ;

Saunders, Christopher T. .

BIOINFORMATICS, 2016, 32 (08) :1220-1222

[7]

Chin CS, 2016, NAT METHODS, V13, P1050, DOI [10.1038/NMETH.4035, 10.1038/nmeth.4035]

[8] Cancer-associated IDH1 mutations produce 2-hydroxyglutarate (vol 462, pg 739, 2010) [J].

Dang, Lenny ;

White, David W. ;

Gross, Stefan ;

Bennett, Bryson D. ;

Bittinger, Mark A. ;

Driggers, Edward M. ;

Fantin, Valeria R. ;

Jang, Hyun Gyung ;

Jin, Shengfang ;

Keenan, Marie C. ;

Marks, Kevin M. ;

Prins, Robert M. ;

Ward, Patrick S. ;

Yen, Katharine E. ;

Liau, Linda M. ;

Rabinowitz, Joshua D. ;

Cantley, Lewis C. ;

Thompson, Craig B. ;

Vander Heiden, Matthew G. ;

Su, Shinsan M. .

NATURE, 2010, 465 (7300) :966-966

[9]

Dolgalev Igor, 2017, F1000Res, V6, P443, DOI 10.12688/f1000research.11254.1

[10] Identification of fusion genes in breast cancer by paired-end RNA-sequencing [J].

Edgren, Henrik ;

Murumagi, Astrid ;

Kangaspeska, Sara ;

Nicorici, Daniel ;

Hongisto, Vesa ;

Kleivi, Kristine ;

Rye, Inga H. ;

Nyberg, Sandra ;

Wolf, Maija ;

Borresen-Dale, Anne-Lise ;

Kallioniemi, Olli .

GENOME BIOLOGY, 2011, 12 (01)

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