ETV1 is a lineage survival factor that cooperates with KIT in gastrointestinal stromal tumours (original) (raw)

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Gene Expression Omnibus

Data deposits

All microarray and ChIP-Seq data are deposited in Gene Expression Omnibus under accession number GSE22852.

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Acknowledgements

This work was supported in part by the National Cancer Institute (K08CA140946, to Y.C.), (5F32CA130372, to P.C.), (CA47179, to C.R.A. and R.G.M.), (CA148260, to R.G.M.), US National Institute of Mental Health (R21MH087840, to D.Z.), National Cancer Institute–American Society of Clinical Oncology Cancer Foundation Clinical Investigator Team Leadership Supplemental Award (to R.G.M.), American Society of Clinical Oncology Young Investigator Award (to P.C.), the Doris Duke (to C.L.S.), Charles H Revson (to Y.C.) and Charles A. Dana (to Y.C.) foundations, The Rockefeller University Fund (to C.D.A.), American Cancer Society Mentored Research Scholar Grant CCE-106841 (to C.R.A.), P01CA47179 (to C.R.A. and R.G.M.), the Life Raft Group (to C.R.A.), the GIST Cancer Research Fund (to C.R.A.), the Shuman Family Fund for GIST Research (to P.C., C.R.A. and R.G.M.), Cycle for Survival (to R.G.M.), Startup Funds from the Albert Einstein College of Medicine (to D.Z.), National Institutes of Health (GM40922, to C.D.A.) and the Starr Cancer Consortium (to P.C., Y.C., C.L.S. and C.D.A.). We thank the International Genomics Consortium for generating ExpO data. We thank G. Wang, P. Iaquinta, and H. Hieronymus for discussions, and especially T. M. Jessell and J. N. Betley for providing and breeding Etv1 −/− mice.

Author information

Author notes

1. Ping Chi, Yu Chen, C. David Allis and Charles L. Sawyers: These authors contributed equally to this work.

Authors and Affiliations

1. Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, 10065, New York, USA
   Ping Chi, Yu Chen & Robert G. Maki
2. Laboratory of Chromatin Biology & Epigenetics, The Rockefeller University, New York, New York, 10065 USA
   Ping Chi & C. David Allis
3. Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, New York, 10065 USA
   Yu Chen, John Wongvipat, Tambudzai Shamu & Charles L. Sawyers
4. Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York, 10065, USA
   Lei Zhang & Cristina R. Antonescu
5. Department of Neurology, Albert Einstein College of Medicine, Bronx, New York, 10461 USA,
   Xingyi Guo & Deyou Zheng
6. Department of Pathology, Brigham and Women’s Hospital, Boston, 02115, Massachusetts, USA
   Jonathan A. Fletcher
7. Genomics Resource Center, The Rockefeller University, New York, 10065, New York, USA
   Scott Dewell
8. Departments of Genetics and Neuroscience, Albert Einstein College of Medicine, Bronx, 10461, New York, USA
   Deyou Zheng
9. Howard Hughes Medical Institute, Chevy Chase, 20815, Maryland, USA
   Charles L. Sawyers

Authors

1. Ping Chi
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2. Yu Chen
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3. Lei Zhang
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4. Xingyi Guo
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5. John Wongvipat
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6. Tambudzai Shamu
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7. Jonathan A. Fletcher
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8. Scott Dewell
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9. Robert G. Maki
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10. Deyou Zheng
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11. Cristina R. Antonescu
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12. C. David Allis
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13. Charles L. Sawyers
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Contributions

Author contributions P.C., Y.C., C.D.A. and C.L.S. designed the experiments. R.G.M. and C.R.A. provided advice about experimental design. P.C. and Y.C. performed most of the experiments, including data mining, data analysis, tissue culture experiments, tissue processing, immunofluorescence microscopy, colony formation assays and ChIP-Seq experiments. J.W. and T.S. performed xenograft and some qRT-PCR experiments. L.Z. and C.R.A. provided human tumour samples and performed fluorescence in situ hybridization and immunohistochemistry on them. S.D. performed the Solexa sequencing and genomic alignment, and X.G. and D.Z. analysed ChIP-Seq data. J.A.F. provided key experimental reagents. P.C., Y.C., C.D.A. and C.L.S. wrote the manuscript. All authors discussed results and edited the manuscript.

Corresponding authors

Correspondence toC. David Allis or Charles L. Sawyers.

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Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Figures

This file contains Supplementary Figures 1-17 with legends. (PDF 14059 kb)

Supplementary Table 1

This table shows a complete gene lists of three GIST-signature gene sets and ICC-MY and ICC-DMP-signature gene sets. Probe ID, gene symbol, average Z-score of expression, and Z-score difference are shown. (XLS 81 kb)

Supplementary Table 2

This table shows gene sets with FDR < 0.25 for overrepresented among downregulated by ETV1 knockdown by GSEA - gene set name, size, enrichment score, normalized enrichment score, p-value, and FDR are shown. (XLS 47 kb)

Supplementary Movie 1

Whole Mount Reconstruction of Kit IF in Etv1+/+ Large Intestine - the movie focuses from the ICC-MY layer through the ICC-IM layer, ending with the ICC-SMP layer. Image is 176x132 μm. (MOV 284 kb)

Supplementary Movie 2

Whole Mount Reconstruction of Kit IF in Etv1-/- Large Intestine ? the movie focuses from the ICC-MY layer through the ICC-IM layer, ending with the ICC-SMP layer. Image is 176x132 μm. (MOV 81 kb)

Supplementary Movie 3

Whole Mount Reconstruction of Kit IF in Etv1+/+ Small Intestine ? the movie focuses from the ICC-MY layer into the ICC-DMP layer. Image is 59x44 μm. (MOV 81 kb)

Supplementary Movie 4

Whole Mount Reconstruction of Kit IF in Etv1-/- Small Intestine - the movie focuses from the ICC-MY layer into the ICC-DMP layer. Image is 59x44 μm. (MOV 25 kb)

Supplementary Movie 5

Whole Mount Reconstruction of Kit IF in Etv1+/+ Cecum - the movie focuses from the ICC-MY layer into the ICC-IM layer. Image is 176x132 μm. (MOV 124 kb)

Supplementary Movie 6

Whole Mount Reconstruction of Kit IF in Etv1-/- Cecum. Movie focuses from the ICC-MY layer into the ICC-IM layer. Image is 176x132 μm. (MOV 26 kb)

Supplementary Movie 7

Whole Mount Reconstruction of Kit IF in Etv1+/+ Gastric Fundus. Movie focuses from the outer longitudinal intramuscular ICC layer into the inner circular intramuscular ICC layer. Image is 176x132 μm. (MOV 104 kb)

Supplementary Movie 8

Whole Mount Reconstruction of Kit IF in Etv1-/- Gastric Fundus. Movie focuses from the outer longitudinal intramuscular ICC layer into the inner circular intramuscular ICC layer. Image is 176x132 μm. (MOV 45 kb)

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Chi, P., Chen, Y., Zhang, L. et al. ETV1 is a lineage survival factor that cooperates with KIT in gastrointestinal stromal tumours.Nature 467, 849–853 (2010). https://doi.org/10.1038/nature09409

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• Received: 04 January 2010
• Accepted: 20 July 2010
• Published: 03 October 2010
• Issue Date: 14 October 2010
• DOI: https://doi.org/10.1038/nature09409