Complementary genomic approaches highlight the PI3K/mTOR pathway as a common vulnerability in osteosarcoma
Open accessAbstract
Significance: We present, to our knowledge, the first comprehensive next-generation sequencing of osteosarcoma in combination with a functional genomic screen in a genetically defined mouse model of osteosarcoma. Our data provide a strong rationale for targeting the phosphatidylinositol 3-kinase/mammalian target of rapamycin pathway in osteosarcoma and a foundation for rational clinical trial design. These findings present an immediate clinical opportunity because multiple inhibitors of this pathway are currently in clinical trials.
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?
The genomic landscape of osteosarcoma tumours is usually dominated by widespread structural rearrangements, suggesting that several mutational mechanisms, including chromothripsis, chromoplexy, kataegis and other structure-altering mechanisms, are involved.
“The genomic landscape of osteosarcoma tumours is usually dominated by widespread structural rearrangements, suggesting that several different mutational mechanisms, including chromothripsis, chromoplexy, kataegis and other structure-altering mechanisms, are involved 32,33,34 .”
From Osteosarcoma (2022) · cites this paper as [34]
Deletion of RB1 occurs in up to 30% of osteosarcoma tumours, often through loss of heterozygosity.
“Deletion of RB1 also occurs in up to 30% of osteosarcoma tumours, often through loss of heterozygosity (LOH) 33,34 .”
From Osteosarcoma (2022) · cites this paper as [34]
Large-scale sequencing has identified only moderate levels of point mutations in osteosarcoma, with few recurrently mutated genes.
“large-scale sequencing has identified only moderate levels of point mutations with few recurrently mutated genes 33,34,36,38 .”
From Osteosarcoma (2022) · cites this paper as [34]
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
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
Self-citationA method and server for predicting damaging missense mutations.
Adzhubei, I. A., Schmidt, S., Peshkin, L., Ramensky, V. E., Gerasimova, A., Bork, P., Kondrashov, A. S., & Sunyaev, S. R. (2010) · Nature Methods · doi:10.1038/nmeth0410-248 · Cited by 13,194 · see citing works
Siegel, R., Naishadham, D., & Jemal, A. (2013) · CA A Cancer Journal for Clinicians · doi:10.3322/caac.21166 · Cited by 11,825 · see citing works
The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity
Barretina, J., Caponigro, G., Stransky, N., Venkatesan, K., Margolin, A. A., Kim, S., Wilson, C. J., Lehár, J., Kryukov, G. V., Sonkin, D., et al. (2012) · Nature · doi:10.1038/nature11003 · Cited by 7,950 · see citing works
Self-citationMutational heterogeneity in cancer and the search for new cancer-associated genes
Lawrence, M. S., Stojanov, P., Polak, P., Kryukov, G. V., Cibulskis, K., Sivachenko, A., Carter, S. L., Stewart, C., Mermel, C. H., Roberts, S. A., et al. (2013) · Nature · doi:10.1038/nature12213 · Cited by 5,461 · see citing works
Self-citationSensitive detection of somatic point mutations in impure and heterogeneous cancer samples
Cibulskis, K., Lawrence, M. S., Carter, S. L., Sivachenko, A., Jaffe, D. B., Sougnez, C. L., Gabriel, S., Meyerson, M. M., Lander, E. S., & Getz, G. A. (2013) · Nature Biotechnology · doi:10.1038/nbt.2514 · Cited by 4,838 · see citing works
Self-citationPredicting Functional Effect of Human Missense Mutations Using PolyPhen‐2
Adzhubei, I., Jordan, D. M., & Sunyaev, S. R. (2013) · Current Protocols in Human Genetics · doi:10.1002/0471142905.hg0720s76 · Cited by 3,705 · 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
Self-citationTargeting PI3K signalling in cancer: opportunities, challenges and limitations
Engelman, J. A. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2664 · Cited by 2,445 · see citing works
Massive genomic rearrangement acquired in a single catastrophic event during cancer development
Stephens, P. J., Greenman, C. D., Fu, B., Yang, F., Bignell, G. R., Mudie, L. J., Pleasance, E. D., Lau, K. W., Beare, D., Stebbings, L. A., et al. (2011) · Cell · doi:10.1016/j.cell.2010.11.055 · Cited by 2,414 · see citing works
COSMIC: exploring the world's knowledge of somatic mutations in human cancer
Forbes, S. A., Beare, D. M., Gunasekaran, P., Leung, K., Bindal, N., Boutselakis, H., Ding, M., Bamford, S., Cole, C. G., Ward, S. A., et al. (2014) · Nucleic Acids Research · doi:10.1093/nar/gku1075 · Cited by 2,261 · see citing works
Mirabello, L., Troisi, R. J., & Savage, S. A. (2009) · Cancer · doi:10.1002/cncr.24121 · Cited by 2,199 · see citing works
Amplification of a gene encoding a p53-associated protein in human sarcomas
Oliner, J. D., Kinzler, K. W., Meltzer, P. S., George, D. L., & Vogelstein, B. (1992) · Nature · doi:10.1038/358080a0 · Cited by 1,949 · see citing works
Mutational Processes Molding the Genomes of 21 Breast Cancers
Nik-Zainal, S., Alexandrov, L. B., Wedge, D. C., Van Loo, P., Greenman, C. D., Raine, K., Jones, D., Hinton, J., Marshall, J., Stebbings, L. A., et al. (2012) · Cell · doi:10.1016/j.cell.2012.04.024 · Cited by 1,909 · see citing works
The genetic basis of early T-cell precursor acute lymphoblastic leukaemia
Zhang, J., Ding, L., Holmfeldt, L., Wu, G., Heatley, S. L., Payne-Turner, D., Easton, J., Chen, X., Wang, J., Rusch, M., et al. (2012) · Nature · doi:10.1038/nature10725 · Cited by 1,596 · cited 1× · see citing works
“Although direct comparison of the number and complexity of the rearrangements seen in OS to other pediatric cancers is not possible, OS appear to have a much greater frequency and complexity of structural variations (38).”
BackgroundPunctuated Evolution of Prostate Cancer Genomes
Baca, S. C., Prandi, D., Lawrence, M. S., Mosquera, J. M., Romanel, A., Drier, Y., Park, K., Kitabayashi, N., MacDonald, T. Y., Ghandi, M., et al. (2013) · Cell · doi:10.1016/j.cell.2013.03.021 · Cited by 1,300 · see citing works
Self-citationLohr, J. G., Stojanov, P., Lawrence, M. S., Auclair, D., Chapuy, B., Sougnez, C. L., Cruz‐Gordillo, P., Knoechel, B., Asmann, Y. W., Slager, S. L., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1121343109 · Cited by 977 · see citing works
Self-citationBissler, J. J., Kingswood, J. C., Radzikowska, E., Zonnenberg, B. A., Frost, M., Белоусова, Е. Д., Sauter, M., Nonomura, N., Brakemeier, S., de Vries, P. J., et al. (2013) · The Lancet · doi:10.1016/s0140-6736(12)61767-x · Cited by 880 · see citing works
Rausch, T., Jones, D. T. W., Zapatka, M., Stütz, A. M., Zichner, T., Weischenfeldt, J., Jäger, N., Remke, M., Shih, D., Northcott, P. A., et al. (2012) · Cell · doi:10.1016/j.cell.2011.12.013 · Cited by 865 · see citing works
Franz, D. N., Belousova, E., Sparagana, S., Bebin, E. M., Frost, M., Kuperman, R., Witt, O., Kohrman, M. H., Flamini, J. R., Wu, J. Y., et al. (2013) · The Lancet · doi:10.1016/s0140-6736(12)61134-9 · Cited by 794 · see citing works
Recurrent Somatic Structural Variations Contribute to Tumorigenesis in Pediatric Osteosarcoma
Chen, X., Bahrami, A., Pappo, A., Easton, J., Dalton, J., Hedlund, E., Ellison, D., Shurtleff, S., Wu, G., Wei, L., et al. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.03.003 · Cited by 752 · see citing works
Highly parallel identification of essential genes in cancer cells
Luo, B., Cheung, H. W., Subramanian, A., Sharifnia, T., Okamoto, M., Yang, X., Hinkle, G., Boehm, J. S., Beroukhim, R., Weir, B. A., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0810485105 · Cited by 541 · see citing works
Self-citationAllen, E. M. V., Wagle, N., Stojanov, P., Perrin, D., Cibulskis, K., Marlow, S., Jané‐Valbuena, J., Friedrich, D. C., Kryukov, G. V., Carter, S. L., et al. (2014) · Nature Medicine · doi:10.1038/nm.3559 · Cited by 533 · see citing works
Self-citationCheung, L. W. T., Hennessy, B. T., Li, J., Yu, S., Myers, A. P., Djordjevic, B., Lu, Y., Stemke‐Hale, K., Dyer, M. D., Zhang, F., et al. (2011) · Cancer Discovery · doi:10.1158/2159-8290.cd-11-0039 · Cited by 471 · see citing works
Mechanisms of sarcoma development
Helman, L. J., & Meltzer, P. S. (2003) · Nature reviews. Cancer · doi:10.1038/nrc1168 · Cited by 460 · see citing works
Osteosarcoma and retinoblastoma: a shared chromosomal mechanism revealing recessive predisposition.
Hansen, M. F., Koufos, A., Gallie, B. L., Phillips, R. A., Fodstad, Ø., Brögger, A., Gedde‐Dahl, T., & Cavenee, W. K. (1985) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.82.18.6216 · Cited by 414 · see citing works
Walkley, C. R., Qudsi, R. A., Sankaran, V. G., Perry, J. A., Gostissa, M., Roth, S. I., Rodda, S. J., Snay, E. R., Dunning, P. S., Fahey, F. H., et al. (2008) · Genes & Development · doi:10.1101/gad.1656808 · Cited by 373 · see citing works
Self-citationA Genome-Scale RNA Interference Screen Implicates NF1 Loss in Resistance to RAF Inhibition
Whittaker, S. R., Theurillat, J.-P. P., Allen, E. M. V., Wagle, N., Hsiao, J., Cowley, G. S., Schadendorf, D., Root, D. E., & Garraway, L. A. (2013) · Cancer Discovery · doi:10.1158/2159-8290.cd-12-0470 · Cited by 360 · see citing works
Self-citationMDM2 gene amplification in metastatic osteosarcoma.
Ladanyi, M., Cha, C. H., Lewis, R., Jhanwar, S. C., Huvos, A. G., & Healey, J. H. (1993) · PubMed · Cited by 342 · see citing works
PathSeq: software to identify or discover microbes by deep sequencing of human tissue
Kostic, A. D., Ojesina, A. I., Pedamallu, C. S., Jung, J., Verhaak, R. G. W., Getz, G. A., & Meyerson, M. M. (2011) · Nature Biotechnology · doi:10.1038/nbt.1868 · Cited by 317 · see citing works
Self-citationMolecular Pathogenesis of Osteosarcoma
Kansara, M., & Thomas, D. M. (2007) · DNA and Cell Biology · doi:10.1089/dna.2006.0505 · Cited by 273 · see citing works
Mutation spectrum of the retinoblastoma gene in osteosarcomas.
Wadayama, B., Toguchida, J., Shimizu, T., Ishizaki, K., Sasaki, M. S., Kotoura, Y., & Yamamuro, T. (1994) · PubMed · Cited by 250 · see citing works
Demetri, G. D., Chawla, S. P., Ray-Coquard, I., Le Cesne, A., Staddon, A. P., Milhem, M. M., Penel, N., Riedel, R. F., Bui-Nguyen, B., Cranmer, L. D., et al. (2013) · Journal of Clinical Oncology · doi:10.1200/jco.2012.45.5766 · Cited by 245 · see citing works
Chawla, S. P., Staddon, A. P., Baker, L. H., Schuetze, S. M., Tolcher, A. W., D’Amato, G. Z., Blay, J., Mita, M. M., Sankhala, K. K., Berk, L., et al. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2011.35.6329 · Cited by 244 · see citing works
Zhao, G., Cai, C., Yang, T.-T., Qiu, X., Liao, B., Li, W., Ji, Z., Zhao, J., Zhao, H., Guo, M., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0053906 · Cited by 225 · see citing works
Rapamycin Inhibits Ezrin-Mediated Metastatic Behavior in a Murine Model of Osteosarcoma
Wan, X., Mendoza, A., Khanna, C., & Helman, L. J. (2005) · Cancer Research · doi:10.1158/0008-5472.can-04-3135 · Cited by 215 · see citing works
Toguchida, J., Ishizaki, K., Sasaki, M. S., Ikenaga, M., Sugimoto, M., Kotoura, Y., & Yamamuro, T. (1988) · PubMed · Cited by 206 · see citing works
Genome-wide association study identifies two susceptibility loci for osteosarcoma
Savage, S. A., Mirabello, L. J., Wang, Z., Gastier, J. M., Gorlick, R. G., Khanna, C., Flanagan, A. M., Tirabosco, R., Andrulis, I. L., Wunder, J. S., et al. (2013) · Nature Genetics · doi:10.1038/ng.2645 · Cited by 200 · see citing works
Germline mutations of the p53 tumor suppressor gene in children with osteosarcoma.
McIntyre, J., Smith‐Sørensen, B., Friend, S. H., Kassell, J., Børresen‐Dale, A., Yan, Y.-X., Russo, C. L., Sato, J., Barbier, N., & Miser, J. (1994) · Journal of Clinical Oncology · doi:10.1200/jco.1994.12.5.925 · Cited by 199 · see citing works
Alterations of thep53, Rb andMDM2 genes in osteosarcoms
Miller, C. W., Aslo, A., Won, A., Tan, M., Lampkin, B. C., & Koefflar, H. P. (1996) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/bf01213553 · Cited by 188 · see citing works
Tsuchiya, T., Sekine, K., Hinohara, S.-I., Namiki, T., Nobori, T., & Kaneko, Y. (2000) · Cancer Genetics and Cytogenetics · doi:10.1016/s0165-4608(99)00255-1 · Cited by 177 · see citing works
Janeway, K. A., Liegl, B., Harlow, A., et al. (2007) · Cancer Research · doi:10.1158/0008-5472.can-07-1938 · Cited by 173 · see citing works
Self-citationp53 and MDM2 alterations in osteosarcomas
Lonardo, F., Ueda, T., Huvos, A. G., Healey, J. H., & Ladanyi, M. (1997) · Cancer · doi:10.1002/(sici)1097-0142(19970415)79:8 · Cited by 147 · see citing works
Drier, Y., Lawrence, M. S., Carter, S. L., Stewart, C., Gabriel, S., Lander, E. S., Meyerson, M. M., Beroukhim, R., & Getz, G. A. (2012) · Genome Research · doi:10.1101/gr.141382.112 · Cited by 147 · see citing works
Self-citationChromoplexy: A New Category of Complex Rearrangements in the Cancer Genome
Shen, M. M. (2013) · Cancer Cell · doi:10.1016/j.ccr.2013.04.025 · Cited by 130 · see citing works
Rea, S. L., Walsh, J. P., Layfield, R., Ratajczak, T., & Xu, J. (2013) · Endocrine Reviews · doi:10.1210/er.2012-1034 · Cited by 123 · see citing works
Mejia‐Guerrero, S., Quejada, M., Gokgoz, N., Gill, M., Parkes, R. K., Wunder, J. S., & Andrulis, I. L. (2010) · Genes, Chromosomes and Cancer · doi:10.1002/gcc.20761 · Cited by 120 · see citing works
Pignochino, Y., Dell’Aglio, C., Basiricò, M., Capozzi, F., Soster, M., Marchiò, S., Bruno, S., Gammaitoni, L., Sangiolo, D., Torchiaro, E., et al. (2013) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-12-2293 · Cited by 107 · see citing works
Navigating the Therapeutic Complexity of PI3K Pathway Inhibition in Melanoma
Kwong, L. N., & Davies, M. A. (2013) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-0142 · Cited by 103 · see citing works
Copy number gains in EGFR and copy number losses in PTEN are common events in osteosarcoma tumors
Freeman, S. S., Allen, S. W., Ganti, R., Wu, J., Ma, J., Su, X., Neale, G. A. M., Dome, J. S., Daw, N. C., & Khoury, J. D. (2008) · Cancer · doi:10.1002/cncr.23782 · Cited by 102 · see citing works
Tumor Suppressor PTEN is Mutated in Canine Osteosarcoma Cell Lines and Tumors
Levine, R. A., Forest, T. W., & Smith, C. (2002) · Veterinary Pathology · doi:10.1354/vp.39-3-372 · Cited by 101 · see citing works
Moriceau, G., Ory, B., Mitrofan, L. M., Riganti, C., Blanchard, F., Brion, R., Charrier, C., Battaglia, S., Pilet, P., Denis, M. G., et al. (2010) · Cancer Research · doi:10.1158/0008-5472.can-10-0578 · Cited by 97 · see citing works
Gobin, B., Baud’huin, M., Lamoureux, F., Ory, B., Charrier, C., Lanel, R., Battaglia, S., Rédiní, F., Lézot, F., Blanchard, F., et al. (2014) · International Journal of Cancer · doi:10.1002/ijc.29040 · Cited by 78 · see citing works
Leung, E. Y., Kim, J. E., Rewcastle, G. W., et al. (2011) · Cancer Biology & Therapy · doi:10.4161/cbt.11.11.15527 · Cited by 77 · see citing works
Differentiation potential of a mouse bone marrow stromal cell line
Allan, E. H., Ho, P. W. M., Umezawa, A., Hata, J.-I., Makishima, F., Gillespie, M. T., & Martin, T. J. (2003) · Journal of Cellular Biochemistry · doi:10.1002/jcb.10614 · Cited by 74 · see citing works
Zhou, Q., Deng, Z., Zhu, Y., Long, H., Zhang, S., & Zhao, J. (2009) · Medical Oncology · doi:10.1007/s12032-009-9365-y · Cited by 74 · see citing works
Seidinger, A. L., Mastellaro, M. J., Fortes, F. P., Assumpção, J. G., Cardinalli, I. A., Ganazza, M. A., Ribeiro, R. C., Brandalise, S. R., Aguiar, S. D. S., & Yunes, J. A. (2010) · Cancer · doi:10.1002/cncr.25826 · Cited by 72 · see citing works
Self-citationChoy, E., Hornicek, F. J., MacConaill, L. E., Harmon, D. C., Tariq, Z., Garraway, L. A., & Duan, Z. (2011) · Cancer · doi:10.1002/cncr.26617 · Cited by 70 · see citing works
Self-citationGobin, B., Battaglia, S., Lanel, R., Chesneau, J., Amiaud, J., Rédiní, F., Ory, B., & Heymann, D. (2013) · Cancer Letters · doi:10.1016/j.canlet.2013.11.017 · Cited by 70 · see citing works
Tsubaki, M., Satou, T., Itoh, T., et al. (2012) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2012.01.024 · Cited by 67 · see citing works
Henriksen, J. M., Ågesen, T. H., Mælandsmo, G. M., Lothe, R. A., Myklebost, O., & Forus, A. (2003) · Oncogene · doi:10.1038/sj.onc.1206671 · Cited by 65 · see citing works
Kuijjer, M. L., van den Akker, B. E. W. M., Hilhorst, R., Mommersteeg, M., Buddingh, E. P., Serra, M., Buerger, H., Hogendoorn, P. C. W., & Cleton-Jansen, A. (2014) · BMC Medical Genomics · doi:10.1186/1755-8794-7-4 · Cited by 62 · see citing works
COPS3 amplification and clinical outcome in osteosarcoma
Yan, T., Wunder, J. S., Gökgöz, N., Gill, M., Eskandarian, S., Parkes, R. K., Bull, S. B., Bell, R. S., & Andrulis, I. L. (2007) · Cancer · doi:10.1002/cncr.22595 · Cited by 59 · see citing works
Wang, K., Zhuang, Y., Liu, C., & Li, Y. (2012) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2012.07.003 · Cited by 45 · see citing works
Genetic determinants of Paget's disease of bone
Ralston, S. H., & Albagha, O. (2011) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2011.06228.x · Cited by 31 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- Miller CW, et al. (1996) Alterations of the p53, Rb and MDM2 genes in osteosarcoma. J Cancer Res Clin Oncol 122(9):559-565.
Cited by
Sorted by citations
Advancing therapy for osteosarcoma
Gill, J., & Gorlick, R. (2021) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-021-00519-8 · Cited by 876 · see citing works
New Horizons in the Treatment of Osteosarcoma
Meltzer, P. S., & Helman, L. J. (2021) · New England Journal of Medicine · doi:10.1056/nejmra2103423 · Cited by 672 · see citing works
Beird, H. C., Bielack, S. S., Flanagan, A. M., Gill, J., Heymann, D., Janeway, K. A., Livingston, J. A., Roberts, R. D., Strauss, S. J., & Gorlick, R. (2022) · Nature Reviews Disease Primers · doi:10.1038/s41572-022-00409-y · Cited by 660 · see citing works
Self-citationMarina, N. M., Smeland, S., Bielack, S. S., Bernstein, M., Jovic, G., Krailo, M. D., Hook, J. M., Arndt, C., van den Berg, H., Brennan, B., et al. (2016) · The Lancet Oncology · doi:10.1016/s1470-2045(16)30214-5 · Cited by 551 · see citing works
Self-citationGenome-Informed Targeted Therapy for Osteosarcoma
Sayles, L. C., Breese, M. R., Koehne, A. L., Leung, S. G., Lee, A. G., Liu, H.-Y., Spillinger, A., Shah, A. T., Tanasa, B., Straessler, K., et al. (2019) · Cancer Discovery · doi:10.1158/2159-8290.cd-17-1152 · Cited by 452 · see citing works
Exome sequencing of osteosarcoma reveals mutation signatures reminiscent of BRCA deficiency
Kovac, M., Blattmann, C., Ribi, S., Smida, J., Mueller, N. S., Engert, F., Castro-Giner, F., Weischenfeldt, J., Kovacova, M., Krieg, A., et al. (2015) · Nature Communications · doi:10.1038/ncomms9940 · Cited by 353 · see citing works
Sarcoma treatment in the era of molecular medicine
Grünewald, T. G., Alonso, M., Avnet, S., Banito, A., Burdach, S., Cidre‐Aranaz, F., Di Pompo, G., Distel, M., Dorado‐Garcia, H., Garcia‐Castro, J., et al. (2020) · EMBO Molecular Medicine · doi:10.15252/emmm.201911131 · Cited by 319 · see citing works
Behjati, S., Tarpey, P. S., Haase, K., Ye, H., Young, M. D., Alexandrov, L. B., Farndon, S. J., Collord, G., Wedge, D. C., Martincorena, I., et al. (2017) · Nature Communications · doi:10.1038/ncomms15936 · Cited by 261 · see citing works
Mirabello, L., Zhu, B., Koster, R., Karlins, E., Dean, M., Yeager, M., Gianferante, M., Spector, L. G., Morton, L. M., Karyadi, D., et al. (2020) · JAMA Oncology · doi:10.1001/jamaoncol.2020.0197 · Cited by 243 · see citing works
Immuno-genomic landscape of osteosarcoma
Wu, C.-C., Beird, H. C., Andrew Livingston, J., Advani, S., Mitra, A., Cao, S., Reuben, A., Ingram, D., Wang, W.-L., Ju, Z., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-14646-w · Cited by 251 · see citing works
Harris, M. H., DuBois, S. G., Glade Bender, J. L., Kim, A., Crompton, B. D., Parker, E., Dumont, I. P., Hong, A. L., Guo, D., Church, A., et al. (2016) · JAMA Oncology · doi:10.1001/jamaoncol.2015.5689 · Cited by 206 · see citing works
Self-citationSuehara, Y., Alex, D., Bowman, A., Middha, S., Zehir, A., Chakravarty, D., Wang, L., Jour, G., Nafa, K., Hayashi, T., et al. (2019) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-18-4032 · Cited by 135 · see citing works
Gardner, H. L., Sivaprakasam, K., Briones, N., Zismann, V., Perdigones, N., Drenner, K., Facista, S., Richholt, R., Liang, W., Aldrich, J., et al. (2019) · Communications Biology · doi:10.1038/s42003-019-0487-2 · Cited by 120 · see citing works
Self-citationRoberts, R. D., Lizardo, M. M., Reed, D. R., Hingorani, P., Glover, J., Allen‐Rhoades, W., Fan, T., Khanna, C., Sweet‐Cordero, E. A., Cash, T., et al. (2019) · Cancer · doi:10.1002/cncr.32351 · Cited by 127 · see citing works
Self-citationKoirala, P., Roth, M. E., Gill, J., Chinai, J. M., Ewart, M. R., Piperdi, S., Geller, D. S., Hoang, B. H., Fatakhova, Y. V., Ghorpade, M., et al. (2016) · Scientific Reports · doi:10.1038/srep31154 · Cited by 100 · see citing works
Tegavivint and the β-Catenin/ALDH Axis in Chemotherapy-Resistant and Metastatic Osteosarcoma
Nomura, M., Rainusso, N., Lee, Y.-C., Dawson, B., Coarfa, C., Han, R., Larson, J. L., Shuck, R., Kurenbekova, L., & Yustein, J. T. (2019) · JNCI: Journal of the National Cancer Institute · doi:10.1093/jnci/djz026 · Cited by 99 · see citing works
GD2 or HER2 targeting T cell engaging bispecific antibodies to treat osteosarcoma
Park, J. A., & Cheung, N.-K. V. (2020) · Journal of Hematology & Oncology · doi:10.1186/s13045-020-01012-y · Cited by 88 · see citing works
Fan, T. M., Roberts, R. D., & Lizardo, M. M. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.00013 · Cited by 90 · see citing works
Aran, V., Devalle, S., Meohas, W., Heringer, M., Cunha Caruso, A., Pinheiro Aguiar, D., Leite Duarte, M. E., & Moura Neto, V. (2021) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2021.103340 · Cited by 87 · see citing works
Detection of circulating tumor DNA in patients with osteosarcoma
Barris, D. M., Weiner, S. B., Dubin, R. A., Fremed, M., Zhang, X., Piperdi, S., Zhang, W., Maqbool, S., Gill, J., Roth, M., et al. (2018) · Oncotarget · doi:10.18632/oncotarget.24268 · Cited by 63 · see citing works
Bishop, M. W., Chang, Y., Krailo, M. D., Meyers, P. A., Provisor, A. J., Schwartz, C. L., Marina, N. M., Teot, L. A., Gebhardt, M. C., Gorlick, R., et al. (2016) · Pediatric Blood & Cancer · doi:10.1002/pbc.26034 · Cited by 52 · see citing works
Self-citationGenomics and the Immune Landscape of Osteosarcoma
Wu, C.-C., & Livingston, J. A. (2020) · Advances in Experimental Medicine and Biology · doi:10.1007/978-3-030-43085-6_2 · Cited by 58 · see citing works
Francis, A. M., Alexander, A., Liu, Y., Vijayaraghavan, S., Low, K. H., Yang, D., Bui, T., Somaiah, N., Ravi, V., Keyomarsi, K., et al. (2017) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-17-0040 · Cited by 54 · see citing works
Ex vivo screen identifies CDK12 as a metastatic vulnerability in osteosarcoma
Bayles, I., Krajewska, M., Pontius, W. D., Saiakhova, A., Morrow, J. J., Bartels, C., Lu, J., Faber, Z. J., Fedorov, Y., Hong, E. S., et al. (2019) · Journal of Clinical Investigation · doi:10.1172/jci127718 · Cited by 46 · see citing works
Loh, A. H. P., Stewart, E., Bradley, C. L., Chen, X., Daryani, V., Stewart, C. F., Calabrese, C., Funk, A., Miller, G., Karlstrom, A., et al. (2019) · Cancer Letters · doi:10.1016/j.canlet.2018.10.033 · Cited by 36 · see citing works
Morrow, J. J., Mendoza, A., Koyen, A., Lizardo, M. M., Ren, L., Waybright, T. J., Hansen, R. J., Gustafson, D. L., Zhou, M., Fan, T. M., et al. (2016) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-16-0326 · Cited by 27 · see citing works
Tharakan, S., Raja, I., Pietraru, A., Sarecha, E., Gresita, A., Petcu, E., Ilyas, A., & Hadjiargyrou, M. (2023) · Gels · doi:10.3390/gels9040274 · Cited by 18 · see citing works
Mills, L. J., Spector, L. G., Largaespada, D. A., & Williams, L. A. (2021) · Biology of Sex Differences · doi:10.1186/s13293-020-00347-y · Cited by 17 · see citing works
Anderson, C. J., Yang, H., Parsons, J., Ahrens, W. A., Jagosky, M. H., Hsu, J. H., Patt, J. C., Kneisl, J. S., & Steuerwald, N. M. (2025) · Clinical Orthopaedics & Related Research · doi:10.1097/corr.0000000000003161 · Cited by 10 · see citing works
Rajan, S., Zaccaria, S., Cannon, M. V., Cam, M., Gross, A. C., Raphael, B. J., & Roberts, R. D. (2021) · doi:10.1101/2021.08.30.458268 · Cited by 33 · see citing works
- Authors
- Perry, J. A., Kiezun, A., Tonzi, P., Van Allen, E. M., Carter, S. L., Baca, S. C., Cowley, G. S., Bhatt, A. S., Rheinbay, E., Pedamallu, C. S., Helman, E., Taylor-Weiner, A., McKenna, A., DeLuca, D. S., Lawrence, M. S., Ambrogio, L., Sougnez, C., Sivachenko, A., Walensky, L. D., Wagle, N., Mora, J., de Torres, C., Lavarino, C., Dos Santos Aguiar, S., Yunes, J. A., Brandalise, S. R., Mercado-Celis, G. E., Melendez-Zajgla, J., Cárdenas-Cardós, R., Velasco-Hidalgo, L., Roberts, C. W. M., Garraway, L. A., Rodriguez-Galindo, C., Gabriel, S. B., Lander, E. S., Golub, T. R., Orkin, S. H., Getz, G., & Janeway, K. A.
- Affiliations
- Dana-Farber/Boston Children's Cancer and Blood Disorders Center (US)
- The Broad Institute of MIT and Harvard, Cambridge, MA 02142;
- Broad Institute (US)
- Dana-Farber Cancer Institute (US)
- Hospital Sant Joan de Déu Barcelona (ES)
- Department of Pediatric Hematology and Oncology, Hospital Sant Joan de Déu, 08950 Barcelona, Spain;
- Department of Pediatric Oncology, Centro Infantil Boldrini, Campinas, 13083-210, Brazil;
- Subdirection of Basic Research, National Institute of Genomic Medicine, 14610, Mexico City, Mexico;
- Department of Oncology, National Institute of Pediatrics, 04530, Mexico City, Mexico;
- Department of Pediatric Oncology, Dana–Farber/Boston Children’s Cancer and Blood Disorders Center, Boston, MA 02215;
- Howard Hughes Medical Institute (US)
- ORCID
- Perry, Jennifer A.
- Carter, Scott L.
- Baca, Sylvan C.
- Cowley, Glenn S.
- Bhatt, Ami S.
- Rheinbay, Esther
- Pedamallu, Chandra Sekhar
- Helman, Elena
- Taylor-Weiner, Amaro
- McKenna, Aaron
- DeLuca, David S.
- Lawrence, Michael S.
- Sivachenko, Andrey
- Walensky, Loren D.
- Wagle, Nikhil
- Mora, Jaume
- Lavarino, Cinzia
- Roberts, Charles W. M.
- Garraway, Levi A.
- Gabriel, Stacey B.
- Lander, Eric S.
- Golub, Todd R.
- Orkin, Stuart H.
- Getz, Gad
- Janeway, Katherine A.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2014-12-15
- Volume
- 111
- Issue
- 51
- Pages
- E5564-73
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4280630
- OpenAlex
- W2115160785
- Cited by
- 481
- References
- 65
- Citations by year
- 2026: 28 · 2025: 22 · 2024: 39 · 2023: 46 · 2022: 37 · 2021: 60 · 2020: 65 · 2019: 45 · 2018: 30 · 2017: 36 · 2016: 44 · 2015: 26 · 2014: 2
- FWCI
- 28.82
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion, other-oa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
- Funders
- Foster Foundation (Research Grant)
- Alex’s Lemonade Stand Foundation for Childhood Cancer (Innovation Award)
- HHS | NIH | National Cancer Institute (NCI) (U01CA105423)
- St. Baldrick’s Foundation (Career Development Award)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Sarcoma Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- osteosarcoma, PI3K/mTOR pathway, therapeutic vulnerabilities, TP53 mutation, somatic mutations, chromosomal rearrangements, genomic instability, intertumoral heterogeneity, shRNA screen, comparative oncology, pathway analysis, PI3K inhibition, mTOR inhibition, cancer cell lines
- MeSH terms
- Bone Neoplasms, Humans, Osteosarcoma, Genome, Human, Tumor Suppressor Protein p53, Germ-Line Mutation, Genetic Heterogeneity, Phosphatidylinositol 3-Kinases, Cell Line, Tumor, Cell Proliferation, TOR Serine-Threonine Kinases
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
