Driver Fusions and Their Implications in the Development and Treatment of Human Cancers

The Fusion Analysis Working Group, The Cancer Genome Atlas Research Network

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Gene fusions represent an important class of somatic alterations in cancer. We systematically investigated fusions in 9,624 tumors across 33 cancer types using multiple fusion calling tools. We identified a total of 25,664 fusions, with a 63% validation rate. Integration of gene expression, copy number, and fusion annotation data revealed that fusions involving oncogenes tend to exhibit increased expression, whereas fusions involving tumor suppressors have the opposite effect. For fusions involving kinases, we found 1,275 with an intact kinase domain, the proportion of which varied significantly across cancer types. Our study suggests that fusions drive the development of 16.5% of cancer cases and function as the sole driver in more than 1% of them. Finally, we identified druggable fusions involving genes such as TMPRSS2, RET, FGFR3, ALK, and ESR1 in 6.0% of cases, and we predicted immunogenic peptides, suggesting that fusions may provide leads for targeted drug and immune therapy. Gao et al. analyze a 9,624 sample TCGA cohort with 33 cancer types to detect gene fusion events. They provide a landscape of fusion events detected, relate fusions to gene expression, focus on kinase fusion structures, examine mutually exclusive mutation and fusion patterns, and highlight fusion druggability.

Original languageEnglish (US)
Pages (from-to)227-238.e3
JournalCell Reports
Volume23
Issue number1
DOIs
StatePublished - Apr 3 2018

Fingerprint

Human Development
Phosphotransferases
Genes
Gene expression
Tumors
Gene Fusion
Neoplasms
Data fusion
Therapeutics
Oncogene Fusion
Peptides
Gene Expression
Gene Dosage
Pharmaceutical Preparations
Drug Therapy
Mutation

Keywords

  • cancer
  • fusion
  • gene fusions
  • RNA
  • translocation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

The Fusion Analysis Working Group, & The Cancer Genome Atlas Research Network (2018). Driver Fusions and Their Implications in the Development and Treatment of Human Cancers. Cell Reports, 23(1), 227-238.e3. https://doi.org/10.1016/j.celrep.2018.03.050

Driver Fusions and Their Implications in the Development and Treatment of Human Cancers. / The Fusion Analysis Working Group; The Cancer Genome Atlas Research Network.

In: Cell Reports, Vol. 23, No. 1, 03.04.2018, p. 227-238.e3.

Research output: Contribution to journalArticle

The Fusion Analysis Working Group & The Cancer Genome Atlas Research Network 2018, 'Driver Fusions and Their Implications in the Development and Treatment of Human Cancers', Cell Reports, vol. 23, no. 1, pp. 227-238.e3. https://doi.org/10.1016/j.celrep.2018.03.050
The Fusion Analysis Working Group, The Cancer Genome Atlas Research Network. Driver Fusions and Their Implications in the Development and Treatment of Human Cancers. Cell Reports. 2018 Apr 3;23(1):227-238.e3. https://doi.org/10.1016/j.celrep.2018.03.050
The Fusion Analysis Working Group ; The Cancer Genome Atlas Research Network. / Driver Fusions and Their Implications in the Development and Treatment of Human Cancers. In: Cell Reports. 2018 ; Vol. 23, No. 1. pp. 227-238.e3.
@article{8b12a13d17b34b3da37c0e711e3f3c05,
title = "Driver Fusions and Their Implications in the Development and Treatment of Human Cancers",
abstract = "Gene fusions represent an important class of somatic alterations in cancer. We systematically investigated fusions in 9,624 tumors across 33 cancer types using multiple fusion calling tools. We identified a total of 25,664 fusions, with a 63{\%} validation rate. Integration of gene expression, copy number, and fusion annotation data revealed that fusions involving oncogenes tend to exhibit increased expression, whereas fusions involving tumor suppressors have the opposite effect. For fusions involving kinases, we found 1,275 with an intact kinase domain, the proportion of which varied significantly across cancer types. Our study suggests that fusions drive the development of 16.5{\%} of cancer cases and function as the sole driver in more than 1{\%} of them. Finally, we identified druggable fusions involving genes such as TMPRSS2, RET, FGFR3, ALK, and ESR1 in 6.0{\%} of cases, and we predicted immunogenic peptides, suggesting that fusions may provide leads for targeted drug and immune therapy. Gao et al. analyze a 9,624 sample TCGA cohort with 33 cancer types to detect gene fusion events. They provide a landscape of fusion events detected, relate fusions to gene expression, focus on kinase fusion structures, examine mutually exclusive mutation and fusion patterns, and highlight fusion druggability.",
keywords = "cancer, fusion, gene fusions, RNA, translocation",
author = "{The Fusion Analysis Working Group} and {The Cancer Genome Atlas Research Network} and Qingsong Gao and Liang, {Wen Wei} and Foltz, {Steven M.} and Gnanavel Mutharasu and Jayasinghe, {Reyka G.} and Song Cao and Liao, {Wen Wei} and Reynolds, {Sheila M.} and Wyczalkowski, {Matthew A.} and Lijun Yao and Lihua Yu and Sun, {Sam Q.} and Caesar-Johnson, {Samantha J.} and Demchok, {John A.} and Ina Felau and Melpomeni Kasapi and Ferguson, {Martin L.} and Hutter, {Carolyn M.} and Sofia, {Heidi J.} and Roy Tarnuzzer and Zhining Wang and Liming Yang and Zenklusen, {Jean C.} and Zhang, {Jiashan (Julia)} and Sudha Chudamani and Jia Liu and Laxmi Lolla and Rashi Naresh and Todd Pihl and Qiang Sun and Yunhu Wan and Ye Wu and Juok Cho and Timothy DeFreitas and Scott Frazer and Nils Gehlenborg and Gad Getz and Heiman, {David I.} and Jaegil Kim and Lawrence, {Michael S.} and Pei Lin and Sam Meier and Noble, {Michael S.} and Gordon Saksena and Doug Voet and Hailei Zhang and Brady Bernard and Gordon Mills and Paul Spellman and George Thomas",
year = "2018",
month = "4",
day = "3",
doi = "10.1016/j.celrep.2018.03.050",
language = "English (US)",
volume = "23",
pages = "227--238.e3",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "1",

}

TY - JOUR

T1 - Driver Fusions and Their Implications in the Development and Treatment of Human Cancers

AU - The Fusion Analysis Working Group

AU - The Cancer Genome Atlas Research Network

AU - Gao, Qingsong

AU - Liang, Wen Wei

AU - Foltz, Steven M.

AU - Mutharasu, Gnanavel

AU - Jayasinghe, Reyka G.

AU - Cao, Song

AU - Liao, Wen Wei

AU - Reynolds, Sheila M.

AU - Wyczalkowski, Matthew A.

AU - Yao, Lijun

AU - Yu, Lihua

AU - Sun, Sam Q.

AU - Caesar-Johnson, Samantha J.

AU - Demchok, John A.

AU - Felau, Ina

AU - Kasapi, Melpomeni

AU - Ferguson, Martin L.

AU - Hutter, Carolyn M.

AU - Sofia, Heidi J.

AU - Tarnuzzer, Roy

AU - Wang, Zhining

AU - Yang, Liming

AU - Zenklusen, Jean C.

AU - Zhang, Jiashan (Julia)

AU - Chudamani, Sudha

AU - Liu, Jia

AU - Lolla, Laxmi

AU - Naresh, Rashi

AU - Pihl, Todd

AU - Sun, Qiang

AU - Wan, Yunhu

AU - Wu, Ye

AU - Cho, Juok

AU - DeFreitas, Timothy

AU - Frazer, Scott

AU - Gehlenborg, Nils

AU - Getz, Gad

AU - Heiman, David I.

AU - Kim, Jaegil

AU - Lawrence, Michael S.

AU - Lin, Pei

AU - Meier, Sam

AU - Noble, Michael S.

AU - Saksena, Gordon

AU - Voet, Doug

AU - Zhang, Hailei

AU - Bernard, Brady

AU - Mills, Gordon

AU - Spellman, Paul

AU - Thomas, George

PY - 2018/4/3

Y1 - 2018/4/3

N2 - Gene fusions represent an important class of somatic alterations in cancer. We systematically investigated fusions in 9,624 tumors across 33 cancer types using multiple fusion calling tools. We identified a total of 25,664 fusions, with a 63% validation rate. Integration of gene expression, copy number, and fusion annotation data revealed that fusions involving oncogenes tend to exhibit increased expression, whereas fusions involving tumor suppressors have the opposite effect. For fusions involving kinases, we found 1,275 with an intact kinase domain, the proportion of which varied significantly across cancer types. Our study suggests that fusions drive the development of 16.5% of cancer cases and function as the sole driver in more than 1% of them. Finally, we identified druggable fusions involving genes such as TMPRSS2, RET, FGFR3, ALK, and ESR1 in 6.0% of cases, and we predicted immunogenic peptides, suggesting that fusions may provide leads for targeted drug and immune therapy. Gao et al. analyze a 9,624 sample TCGA cohort with 33 cancer types to detect gene fusion events. They provide a landscape of fusion events detected, relate fusions to gene expression, focus on kinase fusion structures, examine mutually exclusive mutation and fusion patterns, and highlight fusion druggability.

AB - Gene fusions represent an important class of somatic alterations in cancer. We systematically investigated fusions in 9,624 tumors across 33 cancer types using multiple fusion calling tools. We identified a total of 25,664 fusions, with a 63% validation rate. Integration of gene expression, copy number, and fusion annotation data revealed that fusions involving oncogenes tend to exhibit increased expression, whereas fusions involving tumor suppressors have the opposite effect. For fusions involving kinases, we found 1,275 with an intact kinase domain, the proportion of which varied significantly across cancer types. Our study suggests that fusions drive the development of 16.5% of cancer cases and function as the sole driver in more than 1% of them. Finally, we identified druggable fusions involving genes such as TMPRSS2, RET, FGFR3, ALK, and ESR1 in 6.0% of cases, and we predicted immunogenic peptides, suggesting that fusions may provide leads for targeted drug and immune therapy. Gao et al. analyze a 9,624 sample TCGA cohort with 33 cancer types to detect gene fusion events. They provide a landscape of fusion events detected, relate fusions to gene expression, focus on kinase fusion structures, examine mutually exclusive mutation and fusion patterns, and highlight fusion druggability.

KW - cancer

KW - fusion

KW - gene fusions

KW - RNA

KW - translocation

UR - http://www.scopus.com/inward/record.url?scp=85044744284&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85044744284&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2018.03.050

DO - 10.1016/j.celrep.2018.03.050

M3 - Article

C2 - 29617662

AN - SCOPUS:85044744284

VL - 23

SP - 227-238.e3

JO - Cell Reports

JF - Cell Reports

SN - 2211-1247

IS - 1

ER -