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Cited by 2,546Cancer Genomics and DiagnosticsGene expression and cancer classificationEpigenetics and DNA Methylation

The DOI matches its Crossref record; 58 of the 58 references it cites were found in a registry or an index.

Cell-of-Origin Patterns Dominate the Molecular Classification of 10,000 Tumors from 33 Types of Cancer

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Hoadley, Katherine A., Yau, Christina, Hinoue, Toshinori, Wolf, Denise M., Lazar, Alexander J., Drill, Esther, Shen, Ronglai, Taylor, Alison M., Cherniack, Andrew D., Thorsson, Vésteinn, Akbani, Rehan, Bowlby, Reanne, Wong, Christopher K., Wiznerowicz, Maciej, Sanchez-Vega, Francisco, Robertson, A. Gordon, Schneider, Barbara G., Lawrence, Michael S., Noushmehr, Houtan, Malta, Tathiane M., Caesar-Johnson, Samantha J., Demchok, John A., Felau, Ina, Kasapi, Melpomeni, Ferguson, Martin L., Hutter, Carolyn M., Sofia, Heidi J., Tarnuzzer, Roy, Wang, Zhining, Yang, Liming, Zenklusen, Jean C., Zhang, Jiashan (Julia), Chudamani, Sudha, Liu, Jia, Lolla, Laxmi, Naresh, Rashi, Pihl, Todd, Sun, Qiang, Wan, Yunhu, Wu, Ye, Cho, Juok, DeFreitas, Timothy, Frazer, Scott, Gehlenborg, Nils, Getz, Gad, Heiman, David I., Kim, Jaegil, Lawrence, Michael S., Lin, Pei, Meier, Sam, Noble, Michael S., Saksena, Gordon, Voet, Doug, Zhang, Hailei, Bernard, Brady, Chambwe, Nyasha, Dhankani, Varsha, Knijnenburg, Theo, Kramer, Roger, Leinonen, Kalle, Liu, Yuexin, Miller, Michael, Reynolds, Sheila, Shmulevich, Ilya, Thorsson, Vesteinn, Zhang, Wei, Akbani, Rehan, Broom, Bradley M., Hegde, Apurva M., Ju, Zhenlin, Kanchi, Rupa S., Korkut, Anil, Li, Jun, Liang, Han, Ling, Shiyun, Liu, Wenbin, Lu, Yiling, Mills, Gordon B., Ng, Kwok-Shing, Rao, Arvind, Ryan, Michael, Wang, Jing, Weinstein, John N., Zhang, Jiexin, Abeshouse, Adam, Armenia, Joshua, Chakravarty, Debyani, Chatila, Walid K., de Bruijn, Ino, Gao, Jianjiong, Gross, Benjamin E., Heins, Zachary J., Kundra, Ritika, La, Konnor, Ladanyi, Marc, Luna, Augustin, Nissan, Moriah G., Ochoa, Angelica, Phillips, Sarah M., Reznik, Ed, Sanchez-Vega, Francisco, Sander, Chris, Schultz, Nikolaus, Sheridan, Robert, Sumer, S. 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DOI 10.1016/j.cell.2018.03.022PMC PMC5957518
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Abstract

We conducted comprehensive integrative molecular analyses of the complete set of tumors in The Cancer Genome Atlas (TCGA), consisting of approximately 10,000 specimens and representing 33 types of cancer. We performed molecular clustering using data on chromosome-arm-level aneuploidy, DNA hypermethylation, mRNA, and miRNA expression levels and reverse-phase protein arrays, of which all, except for aneuploidy, revealed clustering primarily organized by histology, tissue type, or anatomic origin. The influence of cell type was evident in DNA-methylation-based clustering, even after excluding sites with known preexisting tissue-type-specific methylation. Integrative clustering further emphasized the dominant role of cell-of-origin patterns. Molecular similarities among histologically or anatomically related cancer types provide a basis for focused pan-cancer analyses, such as pan-gastrointestinal, pan-gynecological, pan-kidney, and pan-squamous cancers, and those related by stemness features, which in turn may inform strategies for future therapeutic development.

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  1. Malta, 2018, Comprehensive analysis of cancer stemness, Cell, 173

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Hoadley, K. A., Yau, C., Hinoue, T., Wolf, D. M., Lazar, A. J., Drill, E., Shen, R., Taylor, A. M., Cherniack, A. D., Thorsson, V., Akbani, R., Bowlby, R., Wong, C. K., Wiznerowicz, M., Sanchez-Vega, F., Robertson, A. G., Schneider, B. G., Lawrence, M. S., Noushmehr, H., Malta, T. M., Caesar-Johnson, S. J., Demchok, J. A., Felau, I., Kasapi, M., Ferguson, M. L., Hutter, C. M., Sofia, H. J., Tarnuzzer, R., Wang, Z., Yang, L., Zenklusen, J. C., Zhang, J. (., Chudamani, S., Liu, J., Lolla, L., Naresh, R., Pihl, T., Sun, Q., Wan, Y., Wu, Y., Cho, J., DeFreitas, T., Frazer, S., Gehlenborg, N., Getz, G., Heiman, D. I., Kim, J., Lawrence, M. S., Lin, P., Meier, S., Noble, M. S., Saksena, G., Voet, D., Zhang, H., Bernard, B., Chambwe, N., Dhankani, V., Knijnenburg, T., Kramer, R., Leinonen, K., Liu, Y., Miller, M., Reynolds, S., Shmulevich, I., Thorsson, V., Zhang, W., Akbani, R., Broom, B. M., Hegde, A. M., Ju, Z., Kanchi, R. S., Korkut, A., Li, J., Liang, H., Ling, S., Liu, W., Lu, Y., Mills, G. B., Ng, K.-S., Rao, A., Ryan, M., Wang, J., Weinstein, J. N., Zhang, J., Abeshouse, A., Armenia, J., Chakravarty, D., Chatila, W. K., de Bruijn, I., Gao, J., Gross, B. E., Heins, Z. J., Kundra, R., La, K., Ladanyi, M., Luna, A., Nissan, M. G., Ochoa, A., Phillips, S. M., Reznik, E., Sanchez-Vega, F., Sander, C., Schultz, N., Sheridan, R., Sumer, S. O., Sun, Y., Taylor, B. S., Wang, J., Zhang, H., Anur, P., Peto, M., Spellman, P., Benz, C., Stuart, J. M., Wong, C. K., Yau, C., Hayes, D. N., Parker, J. S., Wilkerson, M. D., Ally, A., Balasundaram, M., Bowlby, R., Brooks, D., Carlsen, R., Chuah, E., Dhalla, N., Holt, R., Jones, S. J. M., Kasaian, K., Lee, D., Ma, Y., Marra, M. A., Mayo, M., Moore, R. A., Mungall, A. J., Mungall, K., Robertson, A. G., Sadeghi, S., Schein, J. E., Sipahimalani, P., Tam, A., Thiessen, N., Tse, K., Wong, T., Berger, A. C., Beroukhim, R., Cherniack, A. D., Cibulskis, C., Gabriel, S. B., Gao, G. F., Ha, G., Meyerson, M., Schumacher, S. E., Shih, J., Kucherlapati, M. H., Kucherlapati, R. S., Baylin, S., Cope, L., Danilova, L., Bootwalla, M. S., Lai, P. H., Maglinte, D. T., Van Den Berg, D. J., Weisenberger, D. J., Auman, J. T., Balu, S., Bodenheimer, T., Fan, C., Hoadley, K. A., Hoyle, A. P., Jefferys, S. R., Jones, C. D., Meng, S., Mieczkowski, P. A., Mose, L. E., Perou, A. H., Perou, C. M., Roach, J., Shi, Y., Simons, J. V., Skelly, T., Soloway, M. G., Tan, D., Veluvolu, U., Fan, H., Hinoue, T., Laird, P. W., Shen, H., Zhou, W., Bellair, M., Chang, K., Covington, K., Creighton, C. J., Dinh, H., Doddapaneni, H., Donehower, L. A., Drummond, J., Gibbs, R. A., Glenn, R., Hale, W., Han, Y., Hu, J., Korchina, V., Lee, S., Lewis, L., Li, W., Liu, X., Morgan, M., Morton, D., Muzny, D., Santibanez, J., Sheth, M., Shinbrot, E., Wang, L., Wang, M., Wheeler, D. A., Xi, L., Zhao, F., Hess, J., Appelbaum, E. L., Bailey, M., Cordes, M. G., Ding, L., Fronick, C. C., Fulton, L. A., Fulton, R. S., Kandoth, C., Mardis, E. R., McLellan, M. D., Miller, C. A., Schmidt, H. K., Wilson, R. K., Crain, D., Curley, E., Gardner, J., Lau, K., Mallery, D., Morris, S., Paulauskis, J., Penny, R., Shelton, C., Shelton, T., Sherman, M., Thompson, E., Yena, P., Bowen, J., Gastier-Foster, J. M., Gerken, M., Leraas, K. M., Lichtenberg, T. M., Ramirez, N. C., Wise, L., Zmuda, E., Corcoran, N., Costello, T., Hovens, C., Carvalho, A. L., de Carvalho, A. C., Fregnani, J. H., Longatto-Filho, A., Reis, R. M., Scapulatempo-Neto, C., Silveira, H. C. S., Vidal, D. O., Burnette, A., Eschbacher, J., Hermes, B., Noss, A., Singh, R., Anderson, M. L., Castro, P. D., Ittmann, M., Huntsman, D., Kohl, B., Le, X., Thorp, R., Andry, C., Duffy, E. R., Lyadov, V., Paklina, O., Setdikova, G., Shabunin, A., Tavobilov, M., McPherson, C., Warnick, R., Berkowitz, R., Cramer, D., Feltmate, C., Horowitz, N., Kibel, A., Muto, M., Raut, C. P., Malykh, A., Barnholtz-Sloan, J. 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Affiliations
  • University of California, San Francisco (US)
  • Memorial Sloan Kettering Cancer Center (US)
  • Broad Institute (US)
  • Vanderbilt University Medical Center (US)
  • Henry Ford Health (US)
  • Buck Institute for Research on Aging (US)
  • Van Andel Institute (US)
  • BC Cancer Agency (CA)
  • Institute for Systems Biology (US)
  • The University of Texas MD Anderson Cancer Center (US)
  • University of California, Santa Cruz (US)
  • University of North Carolina at Chapel Hill (US)
  • Poznan University of Medical Sciences (PL)
Corresponding author
  • Felau, Ina
  • Nissan, Moriah G.
  • Weisenberger, Daniel J.
  • Jones, Corbin D.
  • Bellair, Michelle
  • Mallery, David
  • Oosterhuis, Wolter
  • Kefford, Richard
  • Vocke, Cathy D.
  • Zuna, Rosemary
  • Rubin, Mark A.
  • Aredes, Natália D.
ORCID
Venue
Cell
Publisher
Elsevier BV
Published
2018-04
Volume
173
Issue
2
Pages
291-304.e6
ISSN
0092-8674 (ISSN-L)
DOI
10.1016/j.cell.2018.03.022
PMC
PMC5957518
OpenAlex
W2796153844
Cited by
2,546
References
58
Citations by year
2026: 284 · 2025: 294 · 2024: 296 · 2023: 355 · 2022: 375 · 2021: 374 · 2020: 330 · 2019: 178 · 2018: 56
FWCI
71.94
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (acceptedVersion, cc-by-nc-nd)
  • Minerva Access (University of Melbourne) (submittedVersion, cc-by-nc-nd)
  • UWA Profiles and Research Repository (UWA) (submittedVersion, cc-by)
  • Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
  • Bern Open Repository and Information System (University of Bern) (submittedVersion, cc-by-nc-nd)
  • Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion)
  • Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
  • eScholarship (California Digital Library) (submittedVersion)
  • Florence Research (University of Florence) (submittedVersion)
  • IRIS Research product catalog (Sapienza University of Rome) (submittedVersion, cc-by-nc-nd)
  • mediaTUM (Technical University of Munich) (submittedVersion, other-oa)
  • Institutional Research Information System University of Ferrara (University of Ferrara) (submittedVersion, cc-by-nc-nd)
  • Spiral (Imperial College London) (submittedVersion, cc-by-nc-nd)
Funders
  • National Human Genome Research Institute
  • National Cancer Institute
  • National Institutes of Health (U24 CA143866, U24 CA143843, P30 CA016672, U24 CA143867, U24 CA143840, U24 CA143882, U24 CA143858, U24 CA143835, U54 HG003273, U24 CA143883, U24 CA143848, U24 CA144025, U24 CA143845, U54 HG003079, U24 CA143799, U54 HG003067)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene expression and cancer classification
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
Keywords
cell of origin, molecular classification of cancer, pan-cancer analysis, TCGA, aneuploidy, DNA methylation, mRNA expression, microRNA expression, reverse phase protein array, histological subtypes, tissue type, stemness, molecular clustering
MeSH terms
Aneuploidy, Chromosomes, Humans, Mutation, Neoplasm Proteins, Neoplasms, RNA, Messenger, Cluster Analysis, Databases, Factual, CpG Islands, DNA Methylation, MicroRNAs

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