Recurrent R-spondin fusions in colon cancer
Open accessAbstract
Exomes, transcriptomes and copy-number alterations in a sample of more than 70 primary human colonic tumours were analysed in an attempt to characterize the genomic landscape; in addition to finding alterations in genes associated with commonly mutated signalling pathways, recurrent gene fusions involving R-spondin family members were also found to occur in approximately 10% of colonic tumours, revealing a potential new therapeutic target. An analysis of exomes, transcriptomes and copy-number alterations in more than 70 primary human colon tumours and matched normal controls has identified more than 35,000 protein-altering somatic mutations, most of which have been validated. In addition to alterations in genes involved in the Wnt pathway, chromatin remodelling and receptor-tyrosine-kinase signalling, the authors identify recurrent gene fusions involving R-spondin family members that collectively occur in 10% of colon tumors; as such they may provide a potential therapeutic target. There is evidence to suggest that these fusions may have a role in the activation of Wnt signalling and tumorigenesis. Identifying and understanding changes in cancer genomes is essential for the development of targeted therapeutics1. Here we analyse systematically more than 70 pairs of primary human colon tumours by applying next-generation sequencing to characterize their exomes, transcriptomes and copy-number alterations. We have identified 36,303 protein-altering somatic changes that include several new recurrent mutations in the Wnt pathway gene TCF7L2, chromatin-remodelling genes such as TET2 and TET3 and receptor tyrosine kinases including ERBB3. Our analysis for significantly mutated cancer genes identified 23 candidates, including the cell cycle checkpoint kinase ATM. Copy-number and RNA-seq data analysis identified amplifications and corresponding overexpression of IGF2 in a subset of colon tumours. Furthermore, using RNA-seq data we identified multiple fusion transcripts including recurrent gene fusions involving R-spondin family members RSPO2 and RSPO3 that together occur in 10% of colon tumours. The RSPO fusions were mutually exclusive with APC mutations, indicating that they probably have a role in the activation of Wnt signalling and tumorigenesis. Consistent with this we show that the RSPO fusion proteins were capable of potentiating Wnt signalling. The R-spondin gene fusions and several other gene mutations identified in this study provide new potential opportunities for therapeutic intervention in colon cancer.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Recurrent mutations, rearrangements, and copy-number alterations have been proposed as therapeutically actionable drivers of colorectal tumorigenesis.
“recurrent mutations, rearrangements, and copy-number alterations have been proposed as therapeutically actionable drivers of colorectal tumorigenesis [129, 130]”
From Primary and acquired resistance to EGFR-targeted therapies in colorectal cancer: impact on future treatment strategies (2014) · cites this paper as [129]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Fast and accurate short read alignment with Burrows-Wheeler transform
Li, H., & Durbin, R. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp324 · Cited by 58,607 · see citing works
Subramanian, A., Tamayo, P., Mootha, V. K., Mukherjee, S., Ebert, B. L., Gillette, M. A., Paulovich, A., Pomeroy, S. L., Golub, T. R., Lander, E. S., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506580102 · Cited by 53,625 · see citing works
Differential expression analysis for sequence count data
Anders, S., & Huber, W. (2010) · Genome Biology · doi:10.1186/gb-2010-11-10-r106 · Cited by 15,581 · see citing works
A framework for variation discovery and genotyping using next-generation DNA sequencing data
DePristo, M. A., Banks, E., Poplin, R. E., Garimella, K. V., Maguire, J., Hartl, C., Philippakis, A., del Angel, G., Rivas, M. A., Hanna, M., et al. (2011) · Nature Genetics · doi:10.1038/ng.806 · Cited by 11,216 · see citing works
Circos: An information aesthetic for comparative genomicsPreprint
Krzywinski, M. I., Schein, J. E., Birol, İ., Connors, J. M., Gascoyne, R. D., Horsman, D. E., Jones, S. J. M., & Marra, M. A. (2009) · Genome Research · doi:10.1101/gr.092759.109 · Cited by 10,838 · see citing works
dbSNP: the NCBI database of genetic variation
Sherry, S. T. (2001) · Nucleic Acids Research · doi:10.1093/nar/29.1.308 · Cited by 7,502 · see citing works
Siegel, R. L., Ward, E., Brawley, O. W., & Jemal, A. (2011) · CA A Cancer Journal for Clinicians · doi:10.3322/caac.20121 · Cited by 4,075 · see citing works
Mermel, C. H., Schumacher, S. E., Hill, B., Meyerson, M. M., Beroukhim, R., & Getz, G. A. (2011) · Genome biology · doi:10.1186/gb-2011-12-4-r41 · Cited by 3,469 · see citing works
The Consensus Coding Sequences of Human Breast and Colorectal Cancers
Sjöblom, T., Jones, S., Wood, L. D., Parsons, D. W., Lin, J., Barber, T. D., Mandelker, D. L., Leary, R. J., Ptak, J., Silliman, N., et al. (2006) · Science · doi:10.1126/science.1133427 · Cited by 3,161 · see citing works
The Genomic Landscapes of Human Breast and Colorectal Cancers
Wood, L. D., Parsons, D. W., Jones, S., Lin, J., Sjöblom, T., Leary, R. J., Shen, D., Boca, S. M., Barber, T., Ptak, J., et al. (2007) · Science · doi:10.1126/science.1145720 · Cited by 2,833 · see citing works
Self-citationGMAP: A genomic mapping and alignment program for mRNA and EST sequences
Wu, T. D., & Watanabe, C. K. (2005) · Bioinformatics · doi:10.1093/bioinformatics/bti310 · Cited by 2,354 · see citing works
Self-citationHuman non-synonymous SNPs: server and survey
Ramensky, V. E. (2002) · Nucleic Acids Research · doi:10.1093/nar/gkf493 · Cited by 2,267 · see citing works
Circular binary segmentation for the analysis of array-based DNA copy number data
Olshen, A. B., Venkatraman, E. S., Lucito, R., & Wigler, M. H. (2004) · Biostatistics · doi:10.1093/biostatistics/kxh008 · Cited by 2,256 · see citing works
RNA sequencing: advances, challenges and opportunities
Ozsolak, F., & Milos, P. M. (2011) · Nature Reviews Genetics · doi:10.1038/nrg2934 · Cited by 2,135 · see citing works
Fast and SNP-tolerant detection of complex variants and splicing in short reads
Wu, T. D., & Nacu, S. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btq057 · Cited by 1,894 · see citing works
Self-citationMolecular Genetics of Colorectal Cancer
Fearon, E. R. (2011) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-011110-130235 · Cited by 1,805 · see citing works
BreakDancer: an algorithm for high-resolution mapping of genomic structural variation
Chen, K., Wallis, J. W., McLellan, M. D., Larson, D. E., Kalicki, J. M., Pohl, C. S., McGrath, S. D., Wendl, M. C., Zhang, Q., Locke, D. P., et al. (2009) · Nature Methods · doi:10.1038/nmeth.1363 · Cited by 1,463 · see citing works
Lgr5 homologues associate with Wnt receptors and mediate R-spondin signalling
de Lau, W., Barker, N., Low, T. Y., Koo, B., Li, V. S. W., Teunissen, H., Kujala, P., Haegebarth, A., Peters, P. J., van de Wetering, M., et al. (2011) · Nature · doi:10.1038/nature10337 · Cited by 1,267 · see citing works
Diverse somatic mutation patterns and pathway alterations in human cancers
Kan, Z., Jaiswal, B. S., Stinson, J., Janakiraman, V., Bhatt, D., Stern, H. M., Yue, P., Haverty, P. M., Bourgon, R., Zheng, J., et al. (2010) · Nature · doi:10.1038/nature09208 · Cited by 1,018 · see citing works
Self-citationA faster circular binary segmentation algorithm for the analysis of array CGH data
Venkatraman, E. S., & Olshen, A. B. (2007) · Bioinformatics · doi:10.1093/bioinformatics/btl646 · Cited by 963 · see citing works
Carmon, K. S., Gong, X. W., Lin, Q., Thomas, A., & Liu, Q. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1106083108 · Cited by 857 · see citing works
Accounting for Human Polymorphisms Predicted to Affect Protein FunctionPreprint
Ng, P. C., & Henikoff, S. (2002) · Genome Research · doi:10.1101/gr.212802 · Cited by 695 · see citing works
Cancer genomics: from discovery science to personalized medicine
Chin, L., Andersen, J. N., & Futreal, P. A. (2011) · Nature Medicine · doi:10.1038/nm.2323 · Cited by 639 · see citing works
Forbes, S. A., Tang, G., Bindal, N., Bamford, S., Dawson, E., Cole, C. G., Kok, C. Y., Jia, M., Ewing, R., Menzies, A. H., et al. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkp995 · Cited by 572 · see citing works
LGR4 and LGR5 are R‐spondin receptors mediating Wnt/β‐catenin and Wnt/PCP signalling
Glinka, A., Dolde, C. E., Kirsch, N., Huang, Y., Kazanskaya, O., Ingelfinger, D., Boutros, M., Cruciat, C., & Niehrs, C. (2011) · EMBO Reports · doi:10.1038/embor.2011.175 · Cited by 565 · see citing works
Morgan, M. T., Anders, S., Lawrence, M. F., Aboyoun, P., Pagès, H., & Gentleman, R. C. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp450 · Cited by 545 · see citing works
Self-citationA Transposon-Based Genetic Screen in Mice Identifies Genes Altered in Colorectal Cancer
Starr, T. K., Allaei, R., Silverstein, K. A. T., Staggs, R. A., Sarver, A. L., Bergemann, T. L., Gupta, M., O’Sullivan, M. G., Matise, I., Dupuy, A. J., et al. (2009) · Science · doi:10.1126/science.1163040 · Cited by 344 · see citing works
Self-citationGenomic sequencing of colorectal adenocarcinomas identifies a recurrent VTI1A-TCF7L2 fusion
Bass, A. J., Lawrence, M. S., Brace, L. E., Ramos, A. H., Drier, Y., Cibulskis, K., Sougnez, C. L., Voet, D., Saksena, G., Sivachenko, A., et al. (2011) · Nature Genetics · doi:10.1038/ng.936 · Cited by 309 · see citing works
Timmermann, B., Kerick, M., Roehr, C., Fischer, A., Isau, M., Boerno, S. T., Wunderlich, A., Barmeyer, C., Seemann, P., Koenig, J., et al. (2010) · PLoS ONE · doi:10.1371/journal.pone.0015661 · Cited by 243 · see citing works
PICNIC: an algorithm to predict absolute allelic copy number variation with microarray cancer data
Greenman, C., Bignell, G. R., Butler, A. P., Edkins, S., Hinton, J., Beare, D. M., Swamy, S., Santarius, T., Chen, L., Widaa, S., et al. (2009) · Biostatistics · doi:10.1093/biostatistics/kxp045 · Cited by 196 · see citing works
March, H. N., Rust, A. G., Wright, N. A., et al. (2011) · Nature Genetics · doi:10.1038/ng.990 · Cited by 190 · see citing works
FOXQ1 Is Overexpressed in Colorectal Cancer and Enhances Tumorigenicity and Tumor Growth
Kaneda, H., Arao, T., Tanaka, K., et al. (2010) · Cancer Research · doi:10.1158/0008-5472.can-09-2161 · Cited by 189 · see citing works
Nacu, Ş., Yuan, W., Kan, Z., Bhatt, D., Rivers, C. S., Stinson, J., Peters, B. A., Modrusan, Z. D., Jung, K., Seshagiri, S., et al. (2011) · BMC Medical Genomics · doi:10.1186/1755-8794-4-11 · Cited by 165 · see citing works
Self-citationInhibition of Wnt signaling by Dishevelled PDZ peptides
Zhang, Y., Appleton, B. A., Wiesmann, C., Lau, T., Costa, M., Hannoush, R. N., & Sidhu, S. S. (2009) · Nature Chemical Biology · doi:10.1038/nchembio.152 · Cited by 163 · see citing works
TET Genes: new players in DNA demethylation and important determinants for stemness
Mohr, F., Döhner, K., Buske, C., & Rawat, V. P. S. (2010) · Experimental Hematology · doi:10.1016/j.exphem.2010.12.004 · Cited by 102 · see citing works
Cellular signaling and biological functions of R-spondins
Yoon, J. K., & Lee, J. (2011) · Cellular Signalling · doi:10.1016/j.cellsig.2011.09.023 · Cited by 94 · see citing works
Fhit Tumor Suppressor: Guardian of The Preneoplastic Genome
Pichiorri, F., Palumbo, T., Suh, S., Okamura, H., Trapasso, F., Ishii, H., Huebner, K., & Croce, C. M. (2008) · Future Oncology · doi:10.2217/14796694.4.6.815 · Cited by 51 · see citing works
Inferring the functional effects of mutation through clusters of mutations in homologous proteins
Yue, P., Forrest, W. F., Kaminker, J. S., Lohr, S., Zhang, Z., & Cavet, G. (2010) · Human Mutation · doi:10.1002/humu.21194 · Cited by 49 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Signatures of mutational processes in human cancer
Initiative, A. P. C. G., Alexandrov, L. B., ICGC Breast Cancer Consortium, ICGC MMML-Seq Consortium, PedBrain, I., Nik-Zainal, S., Wedge, D. C., Aparicio, S. A. J. R., Behjati, S., Biankin, A. V., et al. (2013) · Nature · doi:10.1038/nature12477 · Cited by 9,660 · see citing works
Wnt/β-Catenin Signaling, Disease, and Emerging Therapeutic Modalities
Nusse, R., & Clevers, H. (2017) · Cell · doi:10.1016/j.cell.2017.05.016 · Cited by 4,342 · see citing works
Integrative Clinical Genomics of Advanced Prostate Cancer
Robinson, D., Van Allen, E. M., Wu, Y.-M., Schultz, N., Lonigro, R. J., Mosquera, J.-M., Montgomery, B., Taplin, M.-E., Pritchard, C. C., Attard, G., et al. (2015) · Cell · doi:10.1016/j.cell.2015.05.001 · Cited by 3,645 · see citing works
Batlle, E., & Clevers, H. (2017) · Nature Medicine · doi:10.1038/nm.4409 · Cited by 2,769 · see citing works
Zhan, T., Rindtorff, N., & Boutros, M. (2017) · Oncogene · doi:10.1038/onc.2016.304 · Cited by 2,626 · see citing works
Prospective Derivation of a Living Organoid Biobank of Colorectal Cancer Patients
van de Wetering, M., Francies, H. E., Francis, J. M., Bounova, G., Iorio, F., Pronk, A., van Houdt, W., van Gorp, J., Taylor-Weiner, A., Kester, L., et al. (2015) · Cell · doi:10.1016/j.cell.2015.03.053 · Cited by 2,408 · see citing works
The intestinal crypt, a prototype stem cell compartment
Clevers, H. (2013) · Cell · doi:10.1016/j.cell.2013.07.004 · Cited by 1,223 · see citing works
Fujii, M., Shimokawa, M., Date, S., Takano, A., Matano, M., Nanki, K., Ohta, Y., Toshimitsu, K., Nakazato, Y., Kawasaki, K., et al. (2016) · Cell Stem Cell · doi:10.1016/j.stem.2016.04.003 · Cited by 852 · see citing works
Wnt/β-catenin signaling in cancers and targeted therapies
Yu, F., Yu, C., Li, F., Zuo, Y., Wang, Y., Yao, L., Wu, C., Wang, C., & Ye, L. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00701-5 · Cited by 734 · see citing works
From tumour heterogeneity to advances in precision treatment of colorectal cancer
Punt, C. J. A., Koopman, M., & Vermeulen, L. (2017) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2016.171 · Cited by 654 · see citing works
Genetic Mechanisms of Immune Evasion in Colorectal Cancer
Grasso, C. S., Giannakis, M., Wells, D. K., Hamada, T., Mu, X. J., Quist, M., Nowak, J. A., Nishihara, R., Qian, Z. R., Inamura, K., et al. (2018) · Cancer Discovery · doi:10.1158/2159-8290.cd-17-1327 · Cited by 535 · see citing works
“Supplementary Table 6 shows which genes in Figure 2b were novel with respect to the four previous large-scale whole exome sequencing studies of CRC (1,4,6,21).”
ResultAccurate and efficient detection of gene fusions from RNA sequencing data
Uhrig, S., Ellermann, J., Walther, T., Burkhardt, P., Fröhlich, M., Hutter, B., Toprak, U. H., Neumann, O., Stenzinger, A., Scholl, C., et al. (2021) · Genome Research · doi:10.1101/gr.257246.119 · Cited by 526 · see citing works
Mutations and mechanisms of WNT pathway tumour suppressors in cancer
Bugter, J. M., Fenderico, N., & Maurice, M. M. (2021) · Nature Reviews Cancer · doi:10.1038/s41568-020-00307-z · Cited by 466 · see citing works
Mutational signatures: the patterns of somatic mutations hidden in cancer genomes
Alexandrov, L. B., & Stratton, M. R. (2014) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2013.11.014 · Cited by 488 · see citing works
Mouradov, D., Sloggett, C., Jorissen, R. N., Love, C. G., Li, S., Burgess, A. W., Arango, D., Strausberg, R. L., Buchanan, D., Wormald, S., et al. (2014) · Cancer Research · doi:10.1158/0008-5472.can-14-0013 · Cited by 375 · see citing works
All roads lead to <scp>PP</scp>2A: exploiting the therapeutic potential of this phosphatase
Sangodkar, J., Farrington, C. C., McClinch, K., Galsky, M. D., Kastrinsky, D. B., & Narla, G. (2016) · The FEBS Journal · doi:10.1111/febs.13573 · Cited by 312 · see citing works
Biomarker-guided therapy for colorectal cancer: strength in complexity
Sveen, A., Kopetz, S., & Lothe, R. A. (2020) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-019-0241-1 · Cited by 320 · see citing works
WNT as a Driver and Dependency in Cancer
Parsons, M. J., Tammela, T., & Dow, L. E. (2021) · Cancer Discovery · doi:10.1158/2159-8290.cd-21-0190 · Cited by 257 · see citing works
RSPO2 inhibition of RNF43 and ZNRF3 governs limb development independently of LGR4/5/6
Szenker-Ravi, E., Altunoglu, U., Leushacke, M., Bosso-Lefèvre, C., Khatoo, M., Thi Tran, H., Naert, T., Noelanders, R., Hajamohideen, A., Beneteau, C., et al. (2018) · Nature · doi:10.1038/s41586-018-0118-y · Cited by 190 · see citing works
Aberrant Wnt signaling in multiple myeloma: molecular mechanisms and targeting options
van Andel, H., Kocemba, K. A., Spaargaren, M., & Pals, S. T. (2019) · Leukemia · doi:10.1038/s41375-019-0404-1 · Cited by 188 · see citing works
Herpers, B., Eppink, B., James, M. I., Cortina, C., Cañellas-Socias, A., Boj, S. F., Hernando-Momblona, X., Glodzik, D., Roovers, R. C., van de Wetering, M., et al. (2022) · Nature Cancer · doi:10.1038/s43018-022-00359-0 · Cited by 178 · see citing works
α-Ketoglutarate attenuates Wnt signaling and drives differentiation in colorectal cancer
Tran, T. Q., Hanse, E. A., Habowski, A. N., Li, H., Ishak Gabra, M. B., Yang, Y., Lowman, X. H., Ooi, A. M., Liao, S. Y., Edwards, R. A., et al. (2020) · Nature Cancer · doi:10.1038/s43018-020-0035-5 · Cited by 161 · see citing works
MicroRNAs in the etiology of colorectal cancer: Pathways and clinical implications
Strubberg, A. M., & Madison, B. B. (2017) · Disease Models & Mechanisms · doi:10.1242/dmm.027441 · Cited by 147 · see citing works
R-spondin 3 promotes stem cell recovery and epithelial regeneration in the colon
Harnack, C., Berger, H., Antanaviciute, A., Vidal, R., Sauer, S., Simmons, A., Meyer, T. F., & Sigal, M. (2019) · Nature Communications · doi:10.1038/s41467-019-12349-5 · Cited by 137 · see citing works
Levine, A. J., Jenkins, N. A., & Copeland, N. G. (2019) · Cancer Cell · doi:10.1016/j.ccell.2018.11.009 · Cited by 121 · see citing works
Understanding mutagenesis through delineation of mutational signatures in human cancer
Petljak, M., & Alexandrov, L. B. (2016) · Carcinogenesis · doi:10.1093/carcin/bgw055 · Cited by 110 · see citing works
A pan-cancer organoid platform for precision medicine
Larsen, B. M., Kannan, M., Langer, L. F., Leibowitz, B. D., Bentaieb, A., Cancino, A., Dolgalev, I., Drummond, B. E., Dry, J. R., Ho, C.-S., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109429 · Cited by 105 · see citing works
Leto, S. M., & Trusolino, L. (2014) · Journal of Molecular Medicine · doi:10.1007/s00109-014-1161-2 · Cited by 87 · see citing works
Human Biosample Authentication Using the High-Throughput, Cost-Effective SNPtraceTM System
Liang-Chu, M. M. Y., Yu, M., Haverty, P. M., Koeman, J., Ziegle, J., Lee, M., Bourgon, R., & Neve, R. M. (2015) · PLOS ONE · doi:10.1371/journal.pone.0116218 · Cited by 62 · see citing works
Self-citationSelective targeting of KRAS oncogenic alleles by CRISPR/Cas9 inhibits proliferation of cancer cells
Lee, W., Lee, J. H., Jun, S., Lee, J. H., & Bang, D. (2018) · Scientific Reports · doi:10.1038/s41598-018-30205-2 · Cited by 53 · see citing works
LGR5 is associated with tumor aggressiveness in papillary thyroid cancer
Michelotti, G., Jiang, X., Sosa, J. A., Diehl, A. M., & Henderson, B. B. (2015) · Oncotarget · doi:10.18632/oncotarget.5330 · Cited by 31 · see citing works
Therapeutic Potential of PARP Inhibitors in the Treatment of Gastrointestinal Cancers
Alhusaini, A., Cannon, A., Maher, S. G., Reynolds, J. V., & Lynam-Lennon, N. (2021) · Biomedicines · doi:10.3390/biomedicines9081024 · Cited by 24 · see citing works
- Authors
- Seshagiri, S., Stawiski, E. W., Durinck, S., Modrusan, Z., Storm, E. E., Conboy, C. B., Chaudhuri, S., Guan, Y., Janakiraman, V., Jaiswal, B. S., Guillory, J., Ha, C., Dijkgraaf, G. J. P., Stinson, J., Gnad, F., Huntley, M. A., Degenhardt, J. D., Haverty, P. M., Bourgon, R., Wang, W., Koeppen, H., Gentleman, R., Starr, T. K., Zhang, Z., Largaespada, D. A., Wu, T. D., & de Sauvage, F. J.
- Affiliations
- Genentech (US)
- University of Minnesota (US)
- Corresponding author
- Seshagiri, Somasekar
- ORCID
- Venue
- Nature
- Published
- 2012-08
- Volume
- 488
- Issue
- 7413
- Pages
- 660-664
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3690621
- OpenAlex
- W2083457841
- Cited by
- 960
- References
- 38
- Citations by year
- 2026: 21 · 2025: 26 · 2024: 45 · 2023: 55 · 2022: 60 · 2021: 64 · 2020: 82 · 2019: 80 · 2018: 89 · 2017: 93 · 2016: 94 · 2015: 86 · 2014: 79 · 2013: 70 · 2012: 14
- FWCI
- 26.44
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Nature (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Institutes of Health
- Genentech
- National Cancer Institute (R00CA151672, R01CA134759, R01CA113636, T32CA009138)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Keywords
- colon cancer, RSPO2, RSPO3, Wnt signaling, somatic mutations, TCF7L2, TET2, TET3, HER3, ATM, APC mutation, chromatin remodeling, receptor tyrosine kinase, therapeutic target, fusion transcripts
- MeSH terms
- R-Spondins, Base Sequence, Colonic Neoplasms, DNA-Binding Proteins, Humans, Insulin-Like Growth Factor II, Molecular Sequence Data, Mutation, Proto-Oncogene Proteins, Signal Transduction, Gene Expression Regulation, Neoplastic, Protein Serine-Threonine Kinases, Sequence Analysis, RNA, Genes, APC, Cell Cycle Proteins, Thrombospondins, Polymorphism, Single Nucleotide, Gene Expression Profiling, Receptor, ErbB-3, Tumor Suppressor Proteins, Intercellular Signaling Peptides and Proteins, Dioxygenases, Gene Fusion, Wnt Proteins, Genes, Neoplasm, DNA Copy Number Variations, Transcription Factor 7-Like 2 Protein, Exome, Ataxia Telangiectasia Mutated Proteins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
