A Systematic Analysis of Oncogenic Gene Fusions in Primary Colon Cancer

Cancer Research
Wigard P KloostermanEmile Voest

Abstract

Genomic rearrangements that give rise to oncogenic gene fusions can offer actionable targets for cancer therapy. Here we present a systematic analysis of oncogenic gene fusions among a clinically well-characterized, prospectively collected set of 278 primary colon cancers spanning diverse tumor stages and clinical outcomes. Gene fusions and somatic genetic variations were identified in fresh frozen clinical specimens by Illumina RNA-sequencing, the STAR fusion gene detection pipeline, and GATK RNA-seq variant calling. We considered gene fusions to be pathogenically relevant when recurrent, producing divergent gene expression (outlier analysis), or as functionally important (e.g., kinase fusions). Overall, 2.5% of all specimens were defined as harboring a relevant gene fusion (kinase fusions 1.8%). Novel configurations of BRAF, NTRK3, and RET gene fusions resulting from chromosomal translocations were identified. An R-spondin fusion was found in only one tumor (0.35%), much less than an earlier reported frequency of 10% in colorectal cancers. We also found a novel fusion involving USP9X-ERAS formed by chromothripsis and leading to high expression of ERAS, a constitutively active RAS protein normally expressed only in embryonic s...Continue Reading

References

May 30, 2003·Nature·Kazutoshi TakahashiShinya Yamanaka
Oct 18, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Kengo TakeuchiHiroyuki Mano
May 20, 2009·Bioinformatics·Heng Li, Richard Durbin
Jun 23, 2010·The American Journal of Pathology·Eiji KubotaTakashi Joh
Nov 26, 2010·Annual Review of Pathology·Eric R Fearon
Feb 14, 2012·Nature Medicine·Kengo TakeuchiYuichi Ishikawa
Jul 20, 2012·Nature·UNKNOWN Cancer Genome Atlas Network
Aug 17, 2012·Nature·Somasekar SeshagiriFrederic J de Sauvage
Oct 30, 2012·Bioinformatics·Alexander DobinThomas R Gingeras
Feb 12, 2013·Nature Biotechnology·Kristian CibulskisGad Getz
Mar 28, 2013·Proceedings of the National Academy of Sciences of the United States of America·Angela J SievertAdam C Resnick
Jun 25, 2013·Nature·UNKNOWN Cancer Genome Atlas Research Network
Feb 25, 2014·Nature Reviews. Cancer·Lois M Mulligan
Sep 11, 2014·Nature Communications·Nicolas StranskyChristoph Lengauer
Oct 31, 2014·Nucleic Acids Research·Simon A ForbesPeter J Campbell
Dec 9, 2014·Nature Biotechnology·Christiaan KlijnZemin Zhang
Feb 6, 2015·CA: a Cancer Journal for Clinicians·Lindsey A TorreAhmedin Jemal
Apr 30, 2015·Nature·Jarno DrostHans Clevers
May 23, 2015·Nature Reviews. Cancer·Fredrik MertensFelix Mitelman
Jun 17, 2015·Oncotarget·Anne-France Le RolleVi K Chiu
Jul 7, 2015·Cancer Treatment Reviews·K TamasG A P Hospers
Sep 1, 2015·International Journal of Cancer. Journal International Du Cancer·Jeffrey S RossPhilip J Stephens
Oct 16, 2015·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Scott KopetzLeonard Saltz
Dec 20, 2015·Genome Medicine·Chandan Kumar-SinhaArul M Chinnaiyan
Feb 7, 2016·Cancer Discovery·Emile E Voest, Rene Bernards
Mar 1, 2016·The Journal of Pathology·Shigeki SekineAtsushi Ochiai
May 7, 2016·Nature Medicine·Lillian L SiuEmile E Voest
Aug 3, 2016·Therapeutic Advances in Medical Oncology·Andrew MoriarityPaul McCormick

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Citations

Mar 29, 2018·Scientific Reports·Robert R J Coebergh van den BraakJan N M IJzermans
Nov 4, 2017·Nucleic Acids Research·Xin HuRoel G W Verhaak
Mar 15, 2018·Annals of Oncology : Official Journal of the European Society for Medical Oncology·F PietrantonioC Cremolini
Apr 13, 2018·Annals of Oncology : Official Journal of the European Society for Medical Oncology·C SantosR Salazar
Feb 16, 2019·Genes, Chromosomes & Cancer·Patrick R BlackburnKatherine B Geiersbach
Jul 11, 2019·Nature Reviews. Clinical Oncology·Anita SveenRagnhild A Lothe
Nov 19, 2019·Annals of Oncology : Official Journal of the European Society for Medical Oncology·A AmatuS Siena
Feb 7, 2019·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Jing WangZhiyong Liang
Mar 28, 2019·Histopathology·Taiki HashimotoShigeki Sekine
Nov 17, 2019·International Journal of Molecular Sciences·Filippo PaganiFilippo Pietrantonio
Jun 19, 2019·Virchows Archiv : an International Journal of Pathology·Yasuhiko MizuguchiShigeki Sekine
Apr 25, 2020·Genes·Massimo SantoroFrancesca Carlomagno
Aug 31, 2018·Scientific Reports·Cristian Suárez-CabreraManuel Navarro
Sep 6, 2020·BMC Cancer·R R J Coebergh van den BraakL Vermeulen
Jan 23, 2019·Frontiers in Physiology·Lois M Mulligan
Jan 9, 2020·Molecular Cancer Research : MCR·Christina StanglW P Kloosterman
Jan 6, 2021·International Journal of Molecular Sciences·Qiyuan HanNatalia Y Tretyakova
Aug 20, 2019·Cancer Genetics·Julia Isabelle StaubitzNils Hartmann
Dec 6, 2020·Journal of Hematology & Oncology·Mingye HongHua Zhang
Feb 2, 2021·Frontiers in Oncology·Runjiao ZhangJinpu Yu
Jan 9, 2021·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Harshabad SinghJames M Cleary
Apr 7, 2021·World Journal of Surgical Oncology·Inge van den BergStefan Buettner

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