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1. Pan-cancer analysis of whole genomes

Author

Aaltonen, Lauri A, Abascal, Federico, Abeshouse, Adam, Aburatani, Hiroyuki, Adams, David J, Agrawal, Nishant, Ahn, Keun Soo, Ahn, Sung-Min, Aikata, Hiroshi, Akbani, Rehan, Akdemir, Kadir C, Al-Ahmadie, Hikmat, Al-Sedairy, T, Al-Shahrour, Fatima, Alawi, Malik, Albert, Monique, Aldape, Kenneth, Alexandrov, Ludmil B, Ally, Adrian, Alsop, Kathryn, Alvarez, Eva G, Amary, Fernanda, Amin, Samirkumar B, Aminou, Brice, Ammerpohl, Ole, Anderson, Matthew J, Ang, Yeng, Antonello, Davide, Anur, Pavana, Aparicio, Samuel, Appelbaum, Elizabeth L, Arai, Yasuhito, Aretz, Axel, Arihiro, Koji, Ariizumi, Shun-ichi, Armenia, Joshua, Arnould, Laurent, Asa, Sylvia, Assenov, Yassen, Atwal, Gurnit, Aukema, Sietse, Auman, J Todd, Aure, Miriam RR, Awadalla, Philip, Aymerich, Marta, Bader, Gary D, Baez-Ortega, Adrian, Bailey, Matthew H, Bailey, Peter J, Balasundaram, Miruna, Balu, Saianand, Bandopadhayay, Pratiti, Banks, Rosamonde E, Barbi, Stefano, Barbour, Andrew P, Barenboim, Jonathan, Barnholtz-Sloan, Jill, Barr, Hugh, Barrera, Elisabet, Bartlett, John, Bartolome, Javier, Bassi, Claudio, Bathe, Oliver F, Baumhoer, Daniel, Bavi, Prashant, Baylin, Stephen B, Bazant, Wojciech, Beardsmore, Duncan, Beck, Timothy A, Behjati, Sam, Behren, Andreas, Niu, Beifang, Bell, Cindy, Beltran, Sergi, Benz, Christopher, Berchuck, Andrew, Bergmann, Anke K, Bergstrom, Erik N, Berman, Benjamin P, Berney, Daniel M, Bernhart, Stephan H, Beroukhim, Rameen, Berrios, Mario, Bersani, Samantha, Bertl, Johanna, Betancourt, Miguel, Bhandari, Vinayak, Bhosle, Shriram G, Biankin, Andrew V, Bieg, Matthias, Bigner, Darell, Binder, Hans, Birney, Ewan, Birrer, Michael, Biswas, Nidhan K, Bjerkehagen, Bodil, Bodenheimer, Tom, Boice, Lori, Bonizzato, Giada, and De Bono, Johann S

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Bioinformatics and Computational Biology, Genetics, Oncology and Carcinogenesis, Biotechnology, Cancer Genomics, Human Genome, Prevention, Cancer, 2.1 Biological and endogenous factors, Cell Proliferation, Cellular Senescence, Chromothripsis, Cloud Computing, DNA Mutational Analysis, Evolution, Molecular, Female, Genome, Human, Genomics, Germ-Line Mutation, High-Throughput Nucleotide Sequencing, Humans, Information Dissemination, Male, Mutagenesis, Mutation, Neoplasms, Oncogenes, Promoter Regions, Genetic, RNA Splicing, Reproducibility of Results, Telomerase, Telomere, ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium, General Science & Technology
Abstract

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1-3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10-18.

Published
2020

2. Pan-cancer analysis of whole genomes.

Author

ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium

Subjects
ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium, Telomere, Humans, Neoplasms, Telomerase, Reproducibility of Results, DNA Mutational Analysis, Information Dissemination, Genomics, Evolution, Molecular, Cell Proliferation, RNA Splicing, Mutagenesis, Mutation, Germ-Line Mutation, Oncogenes, Genome, Human, Female, Male, Promoter Regions, Genetic, High-Throughput Nucleotide Sequencing, Cloud Computing, Chromothripsis, Cellular Senescence, Cancer, Genetics, Biotechnology, Prevention, Human Genome, 2.1 Biological and endogenous factors, General Science & Technology
Abstract

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1-3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10-18.

Published
2020

3. Pan-cancer analysis of whole genomes

Author

Campbell, P. J. a., Abpemail, Author, Getz, G. b., C, D, Eemail, Author, Korbel, J. O. f., Gemail, Author, Stuart, hEmail Author, J. M., Jennings, J. L. i., Stein, J, L. D. k., Lemail, Author, Perry, M. D. m., Nahal-Bose, N, Ouellette, H. K. n., B. F. F. o., P, C. H. k., Li, Rheinbay, Q, E. b., E, Nielsen, R, Sgroi, G. P. r., D. C. r., Wu, C. -L. r., Faquin, W. C. r., Deshpande, V. r., Boutros, P. C. k., Q, S, Lazar, T, Hoadley, A. J. u., K. A. v., W, Louis, D. N. r., Dursi, L. J. k., Yung, X, Bailey, C. K. n., M. H. y., Z, Saksena, G. b., Raine, Abp, K. M., Buchhalter, Aa, I., Ab, Ac, Kleinheinz, Aa, K., Schlesner, Ac, Aa, M., Zhang, Ad, Wang, J. n., Ae, W., Wheeler, D. A., Af, Ding, Ag, L. y., Z, Simpson, Ah, J. T. k., Ai, O’Connor, B. D. n., Yakneen, Aj, Ellrott, S. g., Ak, K., Miyoshi, Al, N., Butler, Abp, A. P., Royo, Am, R., Shorser, S. I. k., Vazquez, Am, M., Rausch, An, Tiao, T. g., Waszak, G. b., Rodriguez-Martin, S. M. g., Ao, B., Ap, Aq, Shringarpure, Ar, S., D. -Y., As, Demidov, G. M., At, Au, Av, Delaneau, Aw, O., Ax, Ay, Hayashi, Al, S., Imoto, Habermann, N. g., Segre, A. V. b., Garrison, Az, Abp, E., Cafferkey, A. f., Alvarez, E. G., Ao, Heredia-Genestar, J. M., Ba, Muyas, At, F., Drechsel, At, O., Bruzos, Av, A. L., Ao, Temes, Ao, J., Zamora, Ap, Abp, Baez-Ortega, Bb, A., Kim, H. -L., Bc, Mashl, R. J. z., Bd, Ye, Be, K., Dibiase, Bf, Bg, A., Huang, K. -L. z., Letunic, Bh, Bi, I., Mclellan, M. D. y., Z, Ah, Newhouse, S. J. f., Shmaya, As, T., Kumar, Bj, S., Wedge, Bk, D. C., Bl, Abp, Bm, Wright, M. H., Ar, Yellapantula, V. D., Bn, Gerstein, Bo, Bj, M., Bk, Bp, Khurana, Bq, E., Br, Bs, Marques-Bonet, Bt, Bu, T., Bv, Bw, Navarro, Bx, Bu, A., Bustamante, C. D., Ar, Siebert, By, Bz, R., Nakagawa, Ca, Cb, H., Easton, D. F., Cc, Ossowski, Cd, At, S., Tubio, J. M. C., Ao, De La Vega, F. M., Ar, As, By, Estivill, At, X., Yuen, Ce, Mihaiescu, D. k., Omberg, G. L. n., Cf, L., Ferretti, V. n., Sabarinathan, Cg, Ch, R., Ci, Cj, Pich, Ch, O., Gonzalez-Perez, Cj, Ch, A., Taylor-Weiner, Cj, Ck, A., Fittall, M. W., Cl, Demeulemeester, Cl, J., Tarabichi, Cm, Cl, M., Abp, Roberts, Abp, N. D., Van, Loo, Cl, P., Cortés-Ciriano, Cm, Cn, I., Co, Cp, Urban, L. f., Park, G, Co, P., Zhu, Cp, Cq, B., Pitkänen, E. g., Abp, Y., Saini, Cr, N., Klimczak, L. J., Cs, Weischenfeldt, J. g., Ct, Cu, Sidiropoulos, Cu, N., Alexandrov, L. B., Cv, Abp, Rabionet, At, R., Av, Cw, Escaramis, At, G., Cx, Cy, Bosio, At, Av, Holik, A. Z., At, Susak, At, H., Prasad, Av, Av, A., Erkek, S. g., Calabrese, C. f., Raeder, G, Harrington, B. g., Cz, E., Mayes, Da, S., Turner, Da, D., Juul, Cz, S., Roberts, S. A., Db, Song, Cq, L., Koster, Dc, R., Mirabello, Hua, Cq, X., Tanskanen, T. J., Dd, Tojo, Aq, M., Chen, Bk, J., Aaltonen, De, L. A., Df, Rätsch, Dg, G., Dh, Di, Dj, Dk, Schwarz, Dl, R. F. f., Dm, Dn, Do, Butte, A. J., Dp, Brazma, A. f., Chanock, S. J., Cq, Chatterjee, Dq, N., Stegle, Dr, O. f., G, Harismendy, Ds, Dt, O., Bova, G. S., Du, Gordenin, D. A., Cr, Haan, D. h., Sieverling, Dv, L., Feuerbach, Dw, Chalmers, Dx, D., Joly, Dy, Y., Knoppers, Dy, B., Molnár-Gábor, Dz, F., Phillips, Dy, M., Thorogood, Dy, A., Townend, Dy, D., Goldman, Ea, M., Fonseca, N. A. f., Xiang, Eb, Craft, Q. n., Ea, B., Piñeiro-Yáñez, Ec, E., Muñoz, A. f., Petryszak, R. f., Füllgrabe, A. f., Al-Shahrour, Ec, F., Keays, M. f., Haussler, Ea, D., Weinstein, Ed, Ee, J., Huber, Ef, Valencia, W. g., Am, A., Papatheodorou, Bw, Zhu, I. f., Ea, J., Fan, Ae, Y., Torrents, Am, D., Bieg, Bw, Eg, M., Chen, Eh, Ei, K., Chong, Ej, Z., Cibulskis, K. b., Eils, Aa, R., Ac, Ek, Fulton, El, R. S. y., Z, Gelpi, Ah, J. L., Am, Gonzalez, Em, S. f., G, Gut, I. G., Av, Hach, Bu, En, F., Heinold, Eo, Ac, Hu, Ep, T., Huang, V. k., Hutter, Eh, B., Eq, Er, Jäger, Aa, N., Jung, Es, J., Ep, Y., Lalansingh, C. k., Leshchiner, I. b., Livitz, D. b., E. Z., Ep, Maruvka, Y. E. b., R, Et, Milovanovic, Nielsen, M. M., Eu, Paramasivam, Pedersen, Eh, J. S., Eu, Puiggròs, Ev, Sahinalp, S. C., Eo, Ew, Ex, Sarrafi, Eo, I., Stewart, Ex, Stobbe, C. b., M. D., Av, Wala, Bu, J. A. b., E, Wang, Ey, J. z., Be, Wendl, Ez, M. z., Fa, Werner, Fb, Aa, J., Fc, Wu, Ep, Z., Xue, Ep, H., Yamaguchi, T. N. k., Bn, V., Davis-Dusenbery, Bo, B. N., Fd, Grossman, R. L., Fe, Ff, Y., Heinold, Fg, M. C., Aa, Hinton, Ac, Abp, J., Jones, Abp, D. R., Menzies, Abp, A., Stebbings, Abp, L., Hess, J. M. b., Rosenberg, Et, M. b., R, Dunford, A. J. b., Gupta, M. b., Imielinski, Fh, M., Meyerson, Fi, M. b., E, Beroukhim, Ey, R. b., E, Reimand, Fj, J. k., Q, Dhingra, Br, P., Favero, Bt, Fk, F., Dentro, Bl, S., Abp, Cl, Wintersinger, Fl, J., Fm, Fn, Rudneva, V. g., Park, J. W., Fo, Hong, E. P., Fo, Heo, S. G., Fo, Kahles, Dg, A., Lehmann, K. -V., Dg, Di, Dj, Fp, Fq, Soulette, C. M., Aj, Shiraishi, Al, Y., Liu, Fr, F., Fs, He, Fr, Y., Demircioğlu, Ft, D., Davidson, Fu, N. R., Dg, Dl, Fp, Greger, L. f., Fv, S., Liu, Fw, Fv, D., Stark, Fw, S. G., Dj, Fp, Fx, Zhang, Fy, Amin, S. B., Fz, Ga, Gb, Bailey, Gc, P., Chateigner, A. n., Frenkel-Morgenstern, Gd, M., Hou, Fv, Y., Huska, Fw, M. R., Dm, Kilpinen, Ge, H., Lamaze, F. C. k., Fv, C., Fw, Li, Fv, X., Marin, Fw, M. G., Aj, Markowski, Dm, J., Nandi, Gf, T., Ojesina, A. I., Gg, Gh, Gi, Pan-Hammarström, Fv, Q., Park, Gj, P. J., Co, Pedamallu, Cp, C. S. b., E, Fj, Su, Fv, H., Tan, Fw, Gf, P., Gk, Gl, Teh, Gm, B. T., Gk, Gl, Gm, Gn, Go, Wang, Fv, J., Xiong, Fw, Ye, Yung, Fw, Zhang, C. n., Zheng, Fr, L., Zhu, Awadalla, Fw, P. k., L, Creighton, C. J., Gp, Fv, K., Yang, Fw, Göke, Ft, J., Zhang, Gq, Fr, Z., Brooks, Gr, A. N. b., Aj, Fittall, Ey, Martincorena, Abp, I., Rubio-Perez, Ch, C., Cj, Gs, Eu, M., Schumacher, S. b., Shapira, Gt, O. b., Ey, Tamborero, Ch, D., Mularoni, Cj, Ch, L., Hornshøj, Cj, Eu, H., Deu-Pons, Cj, J., Muiños, Gu, Ch, F., Bertl, Cj, Eu, J., Guo, Gv, Ev, Q., Gonzalez-Perez, Cj, Gw, Xiang, Gx, Q., Bazant, W. f., Barrera, E. f., Al-Sedairy, S. T., Gy, Aretz, Gz, A., Bell, Ha, C., Betancourt, Hb, M., Buchholz, Hc, C., Calvo, Hd, F., Chomienne, He, C., Dunn, Hf, M., Edmonds, Hg, S., Green, Hh, E., Gupta, Hi, S., C. M., Hh, Jegalian, Hj, K., Hk, N., Hl, Y., Hm, Hn, Nakagama, Ho, H., Nettekoven, Hp, G., Planko, Hp, L., Scott, Hk, D., Shibata, Hq, T., Shimizu, Hr, Hs, K., Stratton, Abp, M. R., Yugawa, Hs, T., Tortora, Ht, G., Vijayraghavan, Hu, Hi, K., Zenklusen, J. C., Hv, Hw, D., B. M., Dy, Aminou, B. n., Bartolome, Am, J., Boroevich, K. A., Cb, Boyce, Hx, Buchanan, R. f., Ak, A., Byrne, N. J. n., Hy, Z., Cho, Hz, S., Choi, Ia, W., Clapham, Abp, P., Dow, M. T., Hy, Eils, X, Ek, J., Farcas, El, Hy, C., Fayzullaev, N. n., Flicek, P. f., Heath, A. P., Ib, Hofmann, Ic, O., J. H., Id, Hudson, T. J., Ie, Hübschmann, If, Ac, D., Do, Ek, Ig, Ih, Ivkovic, Ii, S., Jeon, S. -H., Ia, Jiao, W. k., Kabbe, Dj, Fq, Kerssemakers, J. N. A., Aa, Ia, H., Ij, J., Koscher, Ik, M., Koures, Hy, A., Kovacevic, Ii, M., Lawerenz, El, C., Il, J., Mijalkovic, Mijalkovic-Lazic, A. M., Ii, Miyano, Nastic, Nicholson, Ocana, D. f., Ohi, Al, K., Ohno-Machado, Hy, L., Pihl, T. D., Im, Prinz, Radovic, Ii, P., Short, C. f., Sofia, H. J., Hh, Spring, Fe, J., Struck, A. J., Ak, Tijanic, Ii, N., Vicente, Hv, Z., Williams, Woo, Ia, Y., Wright, A. J. k., Yang, Hv, L., Hamilton, M. P., In, Johnson, T. A., Hx, Kahraman, Io, A., Ip, Iq, Kellis, M. b., Polak, Ir, P. b., C, Sallari, E, Sinnott-Armstrong, R. b., N. b., Ar, Von, Mering, Iq, C., Beltran, Is, Av, S., Gerhard, Bu, D. S., It, Av, M., Trotta, Bu, J. -R., Bu, Whalley, J. P., Bu, Niu, Iu, B., Espiritu, S. M. G. k., Gao, Ez, Y., Lalansingh, Iv, Teague, C. M. k., Abp, J. W., Wendl, M. C. z., Fa, Fb, Abascal, Abp, F., Bader, G. D. l., Bandopadhayay, P. b., Iw, Ix, Barenboim, J. k., Brunak, Iy, S., Carlevaro-Fita, Iz, Ja, J., Jb, Jc, Chakravarty, Jd, D., Chan, Je, C. W. Y., Aa, Choi, Dw, J. K., Jf, Diamanti, Jg, K., Fink, Frigola, Jh, Gu, J., Gambacorti-Passerini, Ji, C., Garsed, D. W., Jj, Haradhvala, N. J. b., Harmanci, R, A. O., Bk, Helmy, Jk, Fm, M., Herrmann, Aa, C., Ac, Jl, Hobolth, Ev, A., Hodzic, Gv, Ex, E., Dv, C., Isaev, Dw, K. k., Q, Izarzugaza, J. M. G., Iy, Jb, R., Juul, Jm, R. I., Eu, Kim, J. b., J. K., Jn, Jan, Komorowskijg, Lanzós, Jo, Jb, A., Jc, Jm, Larsson, Dg, E., Lee, Bk, D., Bk, S., Bk, X., Lin, Z. b., Liu, Jp, E. M., Br, Bt, Jq, Lochovsky, Bj, L., Bk, Gb, Lou, Madsen, Bk, Eu, T., Marchal, Jr, K., Martinez-Fundichely, Js, Br, A., Bs, Bt, Mcgillivray, P. D., Bj, Meyerson, Bk, W., Paczkowska, Jt, Park, M. k., Ju, K., Park, Jv, Jw, K., Pons, Jx, T., Pulido-Tamayo, Jr, S., Reyes-Salazar, Js, Ch, I., Reyna, M. A., Jy, Rubin, M. A., Jm, Jz, Ka, Kb, Kc, Salichos, Sander, Bk, Dg, C., Ey, Kd, Schumacher, Ke, S. E. b., Gt, Shackleton, Jj, M., Shen, Ke, C., Shrestha, Kf, Eo, R., Shuai, S. k., Tsunoda, L, Hx, T., Kg, Kh, Umer, Ki, H. M., Jg, Uusküla-Reimand, Kj, Kk, L., Verbeke, Kl, L. P. C., Js, Wadelius, Km, Kn, C., Wadi, L. k., Warrell, Bj, J., Bk, Wu, Ko, G., Kp, J., Zhang, Ez, X., Zhang, Kq, Bk, Y., Kr, Ks, Zhao, Kt, Z., Zou, Ku, L., Lawrence, M. S. b., R, Hx, Raphael, B. J., Jy, P. J., Gc, Craft, D. b., Goldman, Kv, M. J., Ea, Aburatani, Kw, H., Binder, Kx, H., Dinh, Ky, H. Q., Kz, S. C., Av, Hoffmann, Bu, Kx, S., Ky, La, Imbusch, Lb, C. D., Dv, Kretzmer, Ky, H., Laird, Lb, P. W., Lc, Martin-Subero, J. I., Bw, Nagae, Ld, Kw, G., Shen, Le, Lf, H., Ik, Q., Weichenhan, Lg, D., Zhou, Lf, W., Berman, B. P., Kz, Lh, Li, Brors, Dv, B., Er, Lj, Plass, Lg, C., Akdemir, K. C., Ei, Bowtell, D. D. L., Jj, Burns, K. H., Lk, Busanovich, Ll, J. b., Lm, Chan, Ln, K., Dueso-Barroso, Edwards, P. A., Lo, Etemadmoghadam, Lp, Jj, D., Haber, J. E., Lq, D. T. W., Lr, Ls, Ju, Y. S., Jf, Abp, Kazanov, M. D., Lt, Lu, Lv, Koh, Lw, Y., Kumar, Lx, Lee, K. b., E. A., Ly, J. J. -K., Co, Lynch, Cp, A. G., Lo, Lp, Lz, Macintyre, Lo, G., Markowetz, Lo, F., Navarro, Lp, F. C. P., Bj, Pearson, J. V., Ma, Rippe, Mb, Do, K., Scully, Mc, R., Villasante, Am, I., Waddell, Ma, N., Yang, Mb, Md, L., Yao, Fh, X., Yoon, Me, S. -S., Lx, C. -Z. b., E, Ey, Bergstrom, E. N., Mf, Boot, Gl, A., Covington, Mg, Ag, K., Fujimoto, Cb, A., M. N., Gl, Islam, Mg, S. M. A., Cv, Mcpherson, J. R., Gl, Morganella, Mg, Abp, S., Mustonen, Mh, V., Mi, Mj, A. W. T., Mk, Prokopec, S. D. k., Vázquez-García, Bn, I., Ml, Mm, Abp, Wu, Gl, Y., Yousif, Mg, F. k., Yu, Mn, W., Rozen, S. G., Gl, Gm, Mg, Rudneva, V. A. g., S. S., Ar, D. J., Da, Xia, Mo, T., Atwal, G. k., L, Fn, Chang, D. K., Gc, Cooke, Mp, S. L., Gc, Faltas, B. M., Dl, Haider, S. k., Kaiser, V. B., Mq, Karlić, Mr, R., Kato, Ms, M., Kübler, K. b., E, R, Margolin, Martin, Mt, S., Abp, Nik-Zainal, Mu, S., Mv, Mw, Abp, P’Ng, Semple, C. k., C. A., Mq, Smith, Ak, J., Sun, R. X. k., Thai, K. n., D. W., Mx, Yuan, My, Lo, K., Mt, Mz, Biankin, A. V., Gc, Mp, Na, Garraway, Nb, Ey, L., Grimmond, S. M., Nc, Adams, Abp, D. J., Anur, Nd, P., Cao, Ae, S., Christie, E. L., Jj, Cmero, Ne, M., Nf, Ng, Cun, Nh, Y., Dawson, Abp, K. J., S. C., Bl, Deshwar, A. G., Ni, Donmez, Eo, N., Drews, Ex, R. M., Lo, Gerstung, M. f., G, Ha, Haase, G. b., Cl, K., Jerman, L. g., Nj, Ji, Nk, Y., Jolly, Nl, Cl, C., Nm, J., Lee-Six, Abp, H., Malikic, Eo, S., Mitchell, Ex, T. J., Lp, Abp, Nn, Morris, Q. D., Fn, Oesper, No, Np, L., Peifer, Nh, M., Peto, Nq, M., Rosebrock, D. b., Rubanova, Ai, Y., Salcedo, Fn, Sengupta, A. k., Nr, S., Shi, No, R., Shin, S. J., Fy, Spiro, O. b., Vembu, No, S., Wintersinger, Ns, J. A., Fl, T. -P., Nh, Nt, K., Nu, H., Spellman, Nv, P. T., Nw, Weinstein, J. N., Ee, Chen, Ef, Fujita, Cb, M., Han, Kq, L., Hasegawa, Al, T., Komura, Al, M., Ae, J., Mizuno, Nx, S., Shimizu, Al, E., Ny, Xu, Nz, Y., Yamaguchi, Al, R., No, F., Kq, Y., Yoon, C. J., Jf, Yuan, Liang, Ae, H., Alawi, Oa, M., Borozan, Ob, Brewer, I. k., D. S., Oc, Cooper, Od, C. S., Od, Oe, Of, Desai, N. n., Grundhoff, Oa, A., Iskar, Og, Oh, M., Oi, X., Zapatka, Lichter, Eq, P., Alsop, Oh, Jj, K., Bruxner, T. J. C., Jh, Christ, A. N., Jh, Cordner, S. M., Oj, Cowin, P. A., Ok, Drapkin, Ol, R., Fereday, Ok, S., George, Gb, J., Ok, A., Holmes, Ma, O., Hung, Mb, J. A., Om, Kassahn, On, K. S., Jh, Kazakoff, Oo, S. H., Ma, Kennedy, Mb, C. J., Op, Leonard, Oq, C. R., Ma, Mileshkin, Mb, Jj, L., Miller, D. K., Jh, Mp, Or, Arnau, G. M., Ok, Mitchell, Ok, C., Newell, Ma, F., Nones, Mb, Ma, K., Patch, Mb, A. -M., Ma, Quinn, Mb, M. C., Ma, Taylor, Mb, D. F., Jh, Thorne, Ok, H., Traficante, Ok, N., Vedururu, Ok, R., N. M., Mb, Waring, P. M., Os, Wood, Ma, S., Mb, Xu, Ma, Q., Defazio, Mb, Ot, A., Ou, Ov, Anderson, M. J., Jh, Antonello, Ow, D., Barbour, A. P., Ox, Bassi, Oy, Ow, C., Bersani, Oz, S., Cataldo, Oz, I., Chantrill, Pa, L. A., Mp, Chiew, Pb, Y. -E., Ot, Chou, Mp, A., Cingarlini, Pc, Ht, S., Cloonan, Pd, N., Corbo, Pa, V., Davi, Pe, M. V., Pf, Duthie, F. R., Gc, Gill, Pg, A. J., Mp, Graham, Pc, J. S., Gc, Harliwong, Ph, Jh, I., Jamieson, N. B., Gc, Nb, Pi, Johns, A. L., Mp, Kench, Or, J. G., Mp, Pc, Pj, Landoni, Ow, L., Lawlor, R. T., Pa, Mafficini, Pa, A., Merrett, N. D., Ow, Miotto, Pk, Ow, M., Musgrove, E. A., Gc, Nagrial, A. M., Mp, Oien, K. A., Os, Pajic, Pl, Mp, M., Pinese, Pm, M., Robertson, A. J., Jh, Rooman, Mp, I., Rusev, B. C., Pa, Samra, J. S., Ow, Scardoni, Pc, Oz, M., Scarlett, C. J., Mp, Scarpa, Pn, Sereni, Ow, E., Sikora, K. O., Pa, Simbolo, Pe, M., Taschuk, M. L. n., Toon, C. W., Mp, Vicentini, Pa, C., Mp, J., Zeps, Po, N., Behren, Pp, Pq, A., Burke, Pr, H., Cebon, Pq, J., Dagg, R. A., Ps, Paoli-Iseppi, De, Pt, R., Dutton-Regester, Field, M. A., Pu, Fitzgerald, Pv, A., Hersey, Pr, P., Jakrot, Pr, V., Johansson, P. A., Ma, Kakavand, Pt, H., Kefford, R. F., Pw, Lau, L. M. S., Px, Long, G. V., Py, Pickett, H. A., Px, Pritchard, A. L., Ma, Pupo, G. M., Pz, Saw, R. P. M., Py, Schramm, S. -J., Qa, Shang, C. A., Pv, Py, P., Spillane, A. J., Py, Stretch, J. R., Py, Tembe, Ot, V., Thompson, Qa, J. F., Py, Vilain, R. E., Qb, Wilmott, J. S., Py, J. Y., Qc, Hayward, N. K., Ma, Mann, Pr, G. J., Ot, Scolyer, Qd, R. A., Ou, Py, Qb, Bartlett, Qe, Qf, J., Bavi, Qg, Qh, P., Chadwick, D. E., Qi, Chan-Seng-Yue, Qh, M., Cleary, Qh, S., Connor, Qj, A. A., Qj, Czajka, Qk, If, K., Denroche, R. E., Qh, Dhani, N. C., Ql, Eagles, If, J., Gallinger, Qj, Qk, Grant, R. C., Qh, Hedley, Qk, Ql, D., Hollingsworth, M. A., Qm, Jang, G. H., Qh, Kalimuthu, S. -B., Qn, Lungu, Qh, I., Luo, Qo, Mbabaali, X. k., If, F., T. A., Qk, J. K., If, Moore, M. J., Ql, Notta, Qh, F., Pasternack, Qp, If, D., Petersen, G. M., Qq, Roehrl, M. H. A. q., Qh, Qr, Qs, Qt, Sam, If, M., Selander, Qk, I., Serra, Os, S., Shahabi, Qn, S., Thayer, S. P., Qm, Timms, L. E., If, Wilson, G. W. k., Wilson, Qh, J. M., Qh, Wouters, B. G., Qu, J. D., If, Qh, Qv, Beck, T. A. n., Bhandari, Qw, Collins, V. k., C. C., Eo, Fleshner, N. E., Qx, Fox, N. S. k., Fraser, M. k., Heisler, L. E., Qy, Lalonde, E. k., Livingstone, J. k., Meng, Qz, A., Sabelnykova, V. Y. k., Shiah, Y. -J. k., Van der Kwast, Ra, T., Bristow, R. G. q., Rb, Rc, Rd, Re, Ding, Rf, S., Rg, D., Fv, L., Nie, Rg, Y., Xiao, Rh, Xing, Hm, R., Yang, Ri, Rj, Y., Banks, R. E., Rk, Bourque, Rl, G., Brennan, Rm, Rn, P., Letourneau, Ro, L., Riazalhosseini, Rm, Y., Scelo, Rn, G., Vasudev, Rk, N., Viksna, Rp, Rq, J., Lathrop, Rm, M., Tost, Rr, J., Ahn, S. -M., Rs, Aparicio, Rt, S., Arnould, Ru, L., Aure, M. R., Rv, Bhosle, Abp, S. G., Birney, E. f., Borg, Rw, A., Boyault, Rx, S., Brinkman, A. B., Ry, Brock, J. E., Rz, Broeks, Sa, A., Børresen-Dale, A. -L., Rv, Caldas, Sb, C., Chin, Sc, S. -F., Sb, Davies, Sc, Mu, H., Abp, Mv, Desmedt, Sd, C., Dirix, Se, Sf, L., Dronov, Ehinger, Sg, A., Eyfjord, J. E., Sh, Fatima, Gt, A., Foekens, J. A., Si, Futreal, P. A., Sj, Garred, Sk, Ø., Giri, Sl, D. D., Sm, Glodzik, Abp, D., Grabau, Sn, D., Hilmarsdottir, Sh, H., Hooijer, G. K., So, Jacquemier, Sp, J., S. J., Sq, Jonasson, J. G., Sh, Jonkers, Sr, J., H. -Y., Sp, King, T. A., Ss, Knappskog, St, Su, S., Abp, Kong, Sp, G., Krishnamurthy, Sv, S., Lakhani, S. R., Sw, Langerød, Rv, A., Larsimont, Sx, D., H. J., Sq, J. -Y., Sy, M. T. M., Sj, Lingjærde, O. C., Sz, Macgrogan, Ta, G., Martens, J. W. M., Si, O’Meara, Pauporté, He, I., Pinder, Tb, S., Pivot, Tc, X., Provenzano, Td, E., Purdie, C. A., Te, Ramakrishna, Abp, M., Ramakrishnan, Abp, K., Reis-Filho, Sm, J., Richardson, A. L., Gt, Ringnér, Rw, M., Rodriguez, J. B., Am, Rodríguez-González, F. G., Iz, Romieu, Tf, G., Salgado, Os, R., Sauer, Sz, T., Shepherd, Abp, R., Sieuwerts, A. M., Si, Simpson, P. T., Sw, Smid, Si, M., Sotiriou, Span, P. N., Tg, Stefánsson, Ó. A., Th, Stenhouse, Ti, A., Stunnenberg, H. G., Fw, Sweep, Tj, Tk, F., Tan, B. K. T., Tl, Thomas, Tm, G., Thompson, A. M., Ti, Tommasi, Tn, S., Treilleux, To, I., Tutt, Tp, Ueno, N. T., Nv, Van, Laere, Sf, S., Van den Eynden, G. G., Sf, Vermeulen, Sf, P., Viari, Vincent-Salomon, Tj, A., Wong, B. H., Tq, Yates, Abp, X., Van, Deurzen, C. H. M., Tr, van de Vijver, M. J., Os, Van’T, Veer, Ts, L., Ammerpohl, Tt, O., Tu, Tv, Aukema, Tu, S., Tv, Tw, Bergmann, A. K., Tx, Bernhart, S. H., Kx, Ky, Lb, Borkhardt, Ty, A., Borst, Tz, C., Burkhardt, Ua, B., Claviez, Ub, A., Goebler, M. E., Uc, Haake, Tt, A., Haas, Tz, S., Hansmann, Ud, M., Hoell, J. I., Ty, Hummel, Ue, M., Karsch, Uf, D., Klapper, Tw, W., Kneba, Uf, M., Kreuz, Ug, M., Kube, Uh, D., Küppers, Ui, R., Lenze, Ue, D., Loeffler, López, Ca, C., Mantovani-Löffler, Tt, Uj, L., Möller, Uk, P., Ott, Ul, G., Radlwimmer, Oh, B., Richter, Tt, J., Rohde, Tw, Um, M., Rosenstiel, P. C., Un, Rosenwald, Uo, A., Schilhabel, M. B., Un, Schreiber, Up, S., Stadler, P. F., Kx, Staib, Uq, P., Stilgenbauer, Ur, S., Sungalee, S. g., Szczepanowski, Tw, M., Toprak, U. H., Ac, Trümper, Us, L. H. P., Uh, Wagener, Ca, R., Zenz, Tt, Er, T., Hovestadt, Oh, V., Von, Kalle, Do, C., Kool, Korshunov, Lr, Ik, A., Landgraf, Ut, P., Lehrach, Uu, Uv, H., Northcott, P. A., Uw, Pfister, S. M., Ik, Lr, Ux, Reifenberger, Uu, G., Warnatz, H. -J., Uv, Wolf, Uy, S., Yaspo, M. -L., Uv, Assenov, Uz, Y., Gerhauser, Minner, Va, S., Schlomm, Ct, T., Simon, Vb, Vc, R., Sauter, Vc, G., Sültmann, Er, H., Biswas, Vd, N. K., Ve, Maitra, Ve, A., Majumder, P. P., Ve, Sarin, Vf, R., Barbi, Pe, S., Bonizzato, Pa, G., Cantù, Dei, Tos, A. P., Vg, Fassan, Vh, M., Grimaldi, Pa, S., Luchini, Oz, C., Malleo, Ow, G., Marchegiani, Milella, Michele, Ht, M., Paiella, Ow, S., Pea, Ow, A., Pederzoli, Ow, P., Ruzzenente, Salvia, Ow, R., Sperandio, Pa, N., Arai, Hq, Y., Hama, Hq, N., Hiraoka, Vi, N., Hosoda, Hq, F., Nakamura, Hq, H., Ojima, Vj, H., Okusaka, Vk, T., Totoki, Urushidate, Hr, T., Fukayama, Vl, M., Ishikawa, Vm, S., Katai, Vn, H., Katoh, Vm, H., Vm, D., Rokutan, Ms, H., Saito-Adachi, Suzuki, Kw, A., Taniguchi, Vo, Vp, H., Tatsuno, Kw, K., Ushiku, Vl, T., Yachida, Hq, S., Yamamoto, Vq, Kw, S., Aikata, Vr, H., Arihiro, Vr, K., Ariizumi, S. -I., Vs, Chayama, Furuta, Gotoh, Vt, K., Hayami, Vu, S., Hirano, Vv, S., Kawakami, Vr, Y., Maejima, Cb, K., Vv, T., Nakano, Ohdan, Sasaki-Oku, Tanaka, Al, H., Vu, M., Yamamoto, Vs, M., Yamaue, Vu, H., Choo, S. P., Vw, Cutcutache, Gl, I., Khuntikeo, Mg, Ow, N., Ong, Vx, C. K., Vy, Pairojkul, Os, C., Popescu, Vz, I., K. S., Wa, Aymerich, Wb, M., Lopez-Guillermo, Wc, A., López-Otín, Wd, C., Puente, X. S., Wd, Campo, We, E., Amary, Wf, Wg, F., Baumhoer, Wh, D., Behjati, Bjerkehagen, Wh, B., Futreal, Wi, Myklebost, Su, O., Pillay, Wj, N., Tarpey, Wk, P., Tirabosco, Wl, R., Zaikova, Wm, O., Flanagan, A. M., Wn, Boultwood, Wo, J., Bowen, Abp, D. T., Cazzola, Wp, M., A. R., Lp, Hellstrom-Lindberg, Wq, E., Malcovati, Wp, L., Nangalia, Wr, J., Papaemmanuil, Vyas, Ma, P., Ang, Ws, Wt, Y., Barr, Wu, H., Beardsmore, Wv, D., Eldridge, Lo, M., Gossage, Ww, J., Grehan, Mv, N., Hanna, G. B., Wx, Hayes, S. J., Wy, Hupp, Wz, T. R., Xa, Khoo, Xb, D., Lagergren, Wq, J., Lovat, Xc, L. B., Ge, Macrae, Ee, S., O’Donovan, Mv, M., O’Neill, J. R., Xd, Parsons, S. L., Xe, Preston, S. R., Xf, Puig, Xg, S., Roques, Xh, T., Sanders, G. w., Sothi, Xi, S., Tavaré, Lo, S., Tucker, Xj, O., Turkington, Xk, R., Underwood, T. J., Xl, Welch, Xm, I., R. C., Mv, Berney, D. M., Xn, Bono, De, J. S., Oe, Cahill, Xo, D., Camacho, Oe, N., Dennis, N. M., Xo, Dudderidge, Xo, T., Edwards, Xp, S. E., Oe, Fisher, Xo, C., Foster, C. S., Xq, Ghori, Xr, Gill, Ws, P., Gnanapragasam, V. J., Nn, Gundem, Xs, Jq, G., Hamdy, F. C., Xt, Hawkins, Hazell, Xo, S., Howat, Nn, W., Isaacs, W. B., Xu, Karaszi, Ws, K., Kay, J. D., Ge, Xo, V., Kote-Jarai, Oe, Z., Kremeyer, Abp, B., Xo, P., Lambert, Ws, A., Leongamornlert, D. A., Oe, Abp, Livni, Xo, N., Y. -J., Xn, Luxton, Xv, H. J., Ge, Marsden, Ws, L., Massie, C. E., Lo, Matthews, Oe, L., Mayer, Xo, E., Mcdermott, Xw, Abp, U., Merson, Oe, S., Neal, D. E., Lo, Nn, Ng, Xx, A., Nicol, Ogden, Rowe, E. W., Xo, Shah, N. C., Nn, Xo, A., Verrill, Ws, C., Visakorpi, Xy, Du, T., Warren, A. Y., Nn, Whitaker, Xz, H. C., Ge, Xv, H., Van, As, Eeles, R. A., Oe, Abeshouse, Xo, Jq, A., Agrawal, Fe, N., Akbani, Mv, R., Al-Ahmadie, Ya, Jq, H., Albert, Qg, M., Aldape, Oi, K., Ally, Yb, Yc, A., Appelbaum, E. L. z., Armenia, Ge, Yd, J., Asa, Xe, S., Auman, Ye, J. T., Yf, Balasundaram, Yc, M., Balu, S. w., Barnholtz-Sloan, Yg, J., Bathe, Yh, O. F., Yi, Baylin, Yj, S. B., Dr, Benz, Xp, Yk, C., Berchuck, Yl, A., Berrios, Ym, M., Bigner, Yn, D., Birrer, M. r., Bodenheimer, T. w., Boice, Xg, L., Bootwalla, M. S., Ym, Bosenberg, Yo, M., Bowlby, Yc, R., Boyd, Yp, J., Broaddus, R. R., Oi, Yq, M., Brooks, Yc, D., Bullman, S. b., Caesar-Johnson, Fj, S. J., Hv, Carey, T. E., Yr, Carlsen, Cerfolio, Ys, R., Chandan, V. S., Yt, H. -W., Wt, Cherniack, Yd, A. D. b., Ey, Chien, Fj, Yu, J., Cho, J. b., Chuah, Yc, E., Cibulskis, C. b., Cope, Yv, L., Cordes, M. G. z., Curley, Xh, Yw, E., Czerniak, Oi, B., Danilova, Xb, Davis, I. J., Yx, Defreitas, T. b., Demchok, J. A., Hv, Dhalla, Yc, N., Dhir, Yy, R., Doddapaneni, H. V., Ag, El-Naggar, Oi, A., Felau, Xb, Hv, I., Ferguson, M. L., Yz, Finocchiaro, Za, G., Fong, K. M., Zb, Frazer, S. b., Friedman, Zc, W., Fronick, C. C. z., Fulton, Xh, Gabriel, L. A. z., Gao, S. B. b., Gehlenborg, N. b., Gershenwald, Zd, J. E., Ze, Ghossein, Zf, Sm, R., Giama, N. H., Zg, Gibbs, R. A., Ag, Gomez, Zh, C., Govindan, R. y., Hayes, D. N. w., Zi, Zj, Hegde, A. M., Ee, Heiman, Ef, Heins, D. I. b., Jq, Z., Hepperla, A. J. w., Holbrook, Ym, A., Holt, R. A., Yc, Hoyle, A. P. w., Hruban, R. H., Yv, Ag, J., Xg, M., Huntsman, Zk, D., Huse, Jq, J., Iacobuzio-Donahue, C. A., Sm, Ittmann, Zl, M., Jayaseelan, Zm, J. C., Ag, Jefferys, S. R. w., C. D., Zn, S. J. M., Zo, Juhl, Zp, H., Kang, K. J., Zq, Karlan, Zr, B., Kasaian, Zo, K., Kebebew, Zs, E., Kim, Zt, H. K., Zu, Korchina, Ag, V., Kundra, Wt, R., Lai, Yd, P. H., Ym, Lander, E. b., Zv, X., Levine, D. A., Jq, Lewis, Zw, Ag, L., Ley, Zx, T., H. I., Yc, Lin, P. b., Linehan, W. M., Zy, F. F., No, Ef, Y., Lype, Zz, L., Yc, Y., Maglinte, D. T., Ym, Aaa, Mardis, E. R. z., Yp, Aab, Marks, Ow, J., Aac, Marra, M. A., Yc, Matthew, T. J., Aj, Mayo, Mccune, Aad, K., Meier, S. R. b., Meng, S. w., Mieczkowski, P. A. v., Mikkelsen, Aae, T., Miller, C. A. z., Mills, Aaf, G. B., Morrison, Aag, Mose, Moser, L. E. w., C. D., Zg, Mungall, A. J., Yc, Yc, K., Mutch, Aah, D., Muzny, Aai, D. M., Myers, Aaj, J., Newton, Aj, Y., Noble, M. S. b., O’Donnell, Aak, P., Aal, B. P., Ochoa, Aam, J. -W., Parker, Aan, J. S., Pass, Aao, H., Pastore, Pennell, Aap, N. A., Perou, Aaq, C. M., Petrelli, Aar, N., Potapova, Aas, O., Rader, Aat, J. S., Ramalingam, Aau, S., Rathmell, Aav, W. K., Reuter, Sm, V., Reynolds, S. M., Zz, Ringel, Aaw, M., Roach, Aax, J., L. R., Zg, A. G., Yc, Sadeghi, Yc, S., Saller, Aay, C., Sanchez-Vega, Wt, F., Schadendorf, Yd, Eq, D., Aaz, Schein, J. E., Yc, Schmidt, H. K. z., Schultz, Yd, N., Seethala, Aba, R., Senbabaoglu, Dg, Y., Shelton, Yw, T., Shi, Y. w., Shih, J. b., Shmulevich, Fj, Zz, I., Shriver, Abb, C., Signoretti, Fj, S., Abc, Jb, Simons, J. V. w., Singer, Abd, Sipahimalani, Yc, P., Skelly, T. J. v., Smith-McCune, Socci, N. D., Dg, Soloway, Aan, M. G., Sood, Abe, A. K., Tam, Tan, D. v., Tarnuzzer, Hv, R., Thiessen, Abf, R. H., L. B., Xg, Tsao, Xe, M., Umbricht, Ye, Lk, C., Abg, Wv, Van Den Berg, D. J., Ym, Van, Meir, Abh, E. G., Veluvolu, U. v., Voet, D. b., Weinberger, Abi, P., Weisenberger, Wigle, Abj, D., Wilkerson, M. D. v., Wilson, R. K. z., Abk, Winterhoff, Abl, B., Wiznerowicz, Abm, M., Abn, Wong, T. z., Yc, Abo, W., Yau, Zhang, H. b., Yd, H., Hv, J., The ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium View Correspondence (jump link), Medical Oncology, Pathology, IBM, Pharmacyclics, Novartis, Celgene, AstraZeneca, Bayer, Janssen Biotech, University of Chicago, Ipsen, Pfizer, Ono Pharmaceutical, Ariad Pharmaceuticals, Gilead Sciences, Bristol-Myers Squibb, University of St Andrews. School of Medicine, University of St Andrews. Statistics, University of St Andrews. Sir James Mackenzie Institute for Early Diagnosis, University of St Andrews. Cellular Medicine Division, RS: CAPHRI - R4 - Health Inequities and Societal Participation, Metamedica, Háskóli Íslands, University of Iceland, Faculty of Medicine, University of Helsinki, Department of Medical and Clinical Genetics, Research Programs Unit, Lauri Antti Aaltonen / Principal Investigator, ATG - Applied Tumor Genomics, Helsinki Institute of Life Science HiLIFE, Organismal and Evolutionary Biology Research Programme, Helsinki Institute for Information Technology, Institute of Biotechnology, Bioinformatics, Department of Computer Science, STEMM - Stem Cells and Metabolism Research Program, Centre of Excellence in Stem Cell Metabolism, Genome-Scale Biology (GSB) Research Program, Department of Physics, HUS Helsinki and Uusimaa Hospital District, University of Zurich, ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium, Apollo - University of Cambridge Repository, Graduate School, Laboratory Genetic Metabolic Diseases, AGEM - Endocrinology, metabolism and nutrition, AGEM - Inborn errors of metabolism, CCA - Cancer biology and immunology, Campbell, P, Getz, G, Korbel, J, Stuart, J, Jennings, J, Stein, L, Perry, M, Nahal-Bose, H, Ouellette, B, Li, C, Rheinbay, E, Nielsen, G, Sgroi, D, Wu, C, Faquin, W, Deshpande, V, Boutros, P, Lazar, A, Hoadley, K, Louis, D, Dursi, L, Yung, C, Bailey, M, Saksena, G, Raine, K, Buchhalter, I, Kleinheinz, K, Schlesner, M, Zhang, J, Wang, W, Wheeler, D, Ding, L, Simpson, J, O'Connor, B, Yakneen, S, Ellrott, K, Miyoshi, N, Butler, A, Royo, R, Shorser, S, Vazquez, M, Rausch, T, Tiao, G, Waszak, S, Rodriguez-Martin, B, Shringarpure, S, Wu, D, Demidov, G, Delaneau, O, Hayashi, S, Imoto, S, Habermann, N, Segre, A, Garrison, E, Cafferkey, A, Alvarez, E, Heredia-Genestar, J, Muyas, F, Drechsel, O, Bruzos, A, Temes, J, Zamora, J, Baez-Ortega, A, Kim, H, Mashl, R, Ye, K, Dibiase, A, Huang, K, Letunic, I, Mclellan, M, Newhouse, S, Shmaya, T, Kumar, S, Wedge, D, Wright, M, Yellapantula, V, Gerstein, M, Khurana, E, Marques-Bonet, T, Navarro, A, Bustamante, C, Siebert, R, Nakagawa, H, Easton, D, Ossowski, S, Tubio, J, De La Vega, F, Estivill, X, Yuen, D, Mihaiescu, G, Omberg, L, Ferretti, V, Sabarinathan, R, Pich, O, Gonzalez-Perez, A, Taylor-Weiner, A, Fittall, M, Demeulemeester, J, Tarabichi, M, Roberts, N, Van Loo, P, Cortes-Ciriano, I, Urban, L, Park, P, Zhu, B, Pitkanen, E, Li, Y, Saini, N, Klimczak, L, Weischenfeldt, J, Sidiropoulos, N, Alexandrov, L, Rabionet, R, Escaramis, G, Bosio, M, Holik, A, Susak, H, Prasad, A, Erkek, S, Calabrese, C, Raeder, B, Harrington, E, Mayes, S, Turner, D, Juul, S, Roberts, S, Song, L, Koster, R, Mirabello, L, Hua, X, Tanskanen, T, Tojo, M, Chen, J, Aaltonen, L, Ratsch, G, Schwarz, R, Butte, A, Brazma, A, Chanock, S, Chatterjee, N, Stegle, O, Harismendy, O, Bova, G, Gordenin, D, Haan, D, Sieverling, L, Feuerbach, L, Chalmers, D, Joly, Y, Knoppers, B, Molnar-Gabor, F, Phillips, M, Thorogood, A, Townend, D, Goldman, M, Fonseca, N, Xiang, Q, Craft, B, Pineiro-Yanez, E, Munoz, A, Petryszak, R, Fullgrabe, A, Al-Shahrour, F, Keays, M, Haussler, D, Weinstein, J, Huber, W, Valencia, A, Papatheodorou, I, Zhu, J, Fan, Y, Torrents, D, Bieg, M, Chen, K, Chong, Z, Cibulskis, K, Eils, R, Fulton, R, Gelpi, J, Gonzalez, S, Gut, I, Hach, F, Heinold, M, Hu, T, Huang, V, Hutter, B, Jager, N, Jung, J, Kumar, Y, Lalansingh, C, Leshchiner, I, Livitz, D, Ma, E, Maruvka, Y, Milovanovic, A, Nielsen, M, Paramasivam, N, Pedersen, J, Puiggros, M, Sahinalp, S, Sarrafi, I, Stewart, C, Stobbe, M, Wala, J, Wang, J, Wendl, M, Werner, J, Wu, Z, Xue, H, Yamaguchi, T, Davis-Dusenbery, B, Grossman, R, Kim, Y, Hinton, J, Jones, D, Menzies, A, Stebbings, L, Hess, J, Rosenberg, M, Dunford, A, Gupta, M, Imielinski, M, Meyerson, M, Beroukhim, R, Reimand, J, Dhingra, P, Favero, F, Dentro, S, Wintersinger, J, Rudneva, V, Park, J, Hong, E, Heo, S, Kahles, A, Lehmann, K, Soulette, C, Shiraishi, Y, Liu, F, He, Y, Demircioglu, D, Davidson, N, Greger, L, Li, S, Liu, D, Stark, S, Zhang, F, Amin, S, Bailey, P, Chateigner, A, Frenkel-Morgenstern, M, Hou, Y, Huska, M, Kilpinen, H, Lamaze, F, Li, X, Liu, X, Marin, M, Markowski, J, Nandi, T, Ojesina, A, Pan-Hammarstrom, Q, Pedamallu, C, Su, H, Tan, P, Teh, B, Xiong, H, Ye, C, Zhang, X, Zheng, L, Zhu, S, Awadalla, P, Creighton, C, Wu, K, Yang, H, Goke, J, Zhang, Z, Brooks, A, Martincorena, I, Rubio-Perez, C, Juul, M, Schumacher, S, Shapira, O, Tamborero, D, Mularoni, L, Hornshoj, H, Deu-Pons, J, Muinos, F, Bertl, J, Guo, Q, Bazant, W, Barrera, E, Al-Sedairy, S, Aretz, A, Bell, C, Betancourt, M, Buchholz, C, Calvo, F, Chomienne, C, Dunn, M, Edmonds, S, Green, E, Gupta, S, Hutter, C, Jegalian, K, Jones, N, Lu, Y, Nakagama, H, Nettekoven, G, Planko, L, Scott, D, Shibata, T, Shimizu, K, Stratton, M, Yugawa, T, Tortora, G, Vijayraghavan, K, Zenklusen, J, Aminou, B, Bartolome, J, Boroevich, K, Boyce, R, Buchanan, A, Byrne, N, Chen, Z, Cho, S, Choi, W, Clapham, P, Dow, M, Eils, J, Farcas, C, Fayzullaev, N, Flicek, P, Heath, A, Hofmann, O, Hong, J, Hudson, T, Hubschmann, D, Ivkovic, S, Jeon, S, Jiao, W, Kabbe, R, Kerssemakers, J, Kim, J, Koscher, M, Koures, A, Kovacevic, M, Lawerenz, C, Liu, J, Mijalkovic, S, Mijalkovic-Lazic, A, Miyano, S, Nastic, M, Nicholson, J, Ocana, D, Ohi, K, Ohno-Machado, L, Pihl, T, Prinz, M, Radovic, P, Short, C, Sofia, H, Spring, J, Struck, A, Tijanic, N, Vicente, D, Wang, Z, Williams, A, Woo, Y, Wright, A, Yang, L, Hamilton, M, Johnson, T, Kahraman, A, Kellis, M, Polak, P, Sallari, R, Sinnott-Armstrong, N, von Mering, C, Beltran, S, Gerhard, D, Gut, M, Trotta, J, Whalley, J, Niu, B, Espiritu, S, Gao, S, Huang, Y, Teague, J, Abascal, F, Bader, G, Bandopadhayay, P, Barenboim, J, Brunak, S, Carlevaro-Fita, J, Chakravarty, D, Chan, C, Choi, J, Diamanti, K, Fink, J, Frigola, J, Gambacorti Passerini, C, Garsed, D, Haradhvala, N, Harmanci, A, Helmy, M, Herrmann, C, Hobolth, A, Hodzic, E, Hong, C, Isaev, K, Izarzugaza, J, Johnson, R, Juul, R, Jan, K, Lanzos, A, Larsson, E, Lee, D, Lin, Z, Liu, E, Lochovsky, L, Lou, S, Madsen, T, Marchal, K, Martinez-Fundichely, A, Mcgillivray, P, Meyerson, W, Paczkowska, M, Park, K, Pons, T, Pulido-Tamayo, S, Reyes-Salazar, I, Reyna, M, Rubin, M, Salichos, L, Sander, C, Shackleton, M, Shen, C, Shrestha, R, Shuai, S, Tsunoda, T, Umer, H, Uuskula-Reimand, L, Verbeke, L, Wadelius, C, Wadi, L, Warrell, J, Wu, G, Yu, J, Zhang, Y, Zhao, Z, Zou, L, Lawrence, M, Raphael, B, Craft, D, Aburatani, H, Binder, H, Dinh, H, Heath, S, Hoffmann, S, Imbusch, C, Kretzmer, H, Laird, P, Martin-Subero, J, Nagae, G, Shen, H, Wang, Q, Weichenhan, D, Zhou, W, Berman, B, Brors, B, Plass, C, Akdemir, K, Bowtell, D, Burns, K, Busanovich, J, Chan, K, Dueso-Barroso, A, Edwards, P, Etemadmoghadam, D, Haber, J, Ju, Y, Kazanov, M, Koh, Y, Kumar, K, Lee, E, Lee, J, Lynch, A, Macintyre, G, Markowetz, F, Navarro, F, Pearson, J, Rippe, K, Scully, R, Villasante, I, Waddell, N, Yao, X, Yoon, S, Zhang, C, Bergstrom, E, Boot, A, Covington, K, Fujimoto, A, Huang, M, Islam, S, Mcpherson, J, Morganella, S, Mustonen, V, Ng, A, Prokopec, S, Vazquez-Garcia, I, Wu, Y, Yousif, F, Yu, W, Rozen, S, Xia, T, Atwal, G, Chang, D, Cooke, S, Faltas, B, Haider, S, Kaiser, V, Karlic, R, Kato, M, Kubler, K, Margolin, A, Martin, S, Nik-Zainal, S, P'Ng, C, Semple, C, Smith, J, Sun, R, Thai, K, Wright, D, Yuan, K, Biankin, A, Garraway, L, Grimmond, S, Adams, D, Anur, P, Cao, S, Christie, E, Cmero, M, Cun, Y, Dawson, K, Deshwar, A, Donmez, N, Drews, R, Gerstung, M, Ha, G, Haase, K, Jerman, L, Ji, Y, Jolly, C, Lee-Six, H, Malikic, S, Mitchell, T, Morris, Q, Oesper, L, Peifer, M, Peto, M, Rosebrock, D, Rubanova, Y, Salcedo, A, Sengupta, S, Shi, R, Shin, S, Spiro, O, Vembu, S, Yang, T, Yu, K, Zhu, H, Spellman, P, Chen, Y, Fujita, M, Han, L, Hasegawa, T, Komura, M, Li, J, Mizuno, S, Shimizu, E, Wang, Y, Xu, Y, Yamaguchi, R, Yang, F, Yang, Y, Yoon, C, Yuan, Y, Liang, H, Alawi, M, Borozan, I, Brewer, D, Cooper, C, Desai, N, Grundhoff, A, Iskar, M, Su, X, Zapatka, M, Lichter, P, Alsop, K, Bruxner, T, Christ, A, Cordner, S, Cowin, P, Drapkin, R, Fereday, S, George, J, Hamilton, A, Holmes, O, Hung, J, Kassahn, K, Kazakoff, S, Kennedy, C, Leonard, C, Mileshkin, L, Miller, D, Arnau, G, Mitchell, C, Newell, F, Nones, K, Patch, A, Quinn, M, Taylor, D, Thorne, H, Traficante, N, Vedururu, R, Waring, P, Wood, S, Xu, Q, Defazio, A, Anderson, M, Antonello, D, Barbour, A, Bassi, C, Bersani, S, Cataldo, I, Chantrill, L, Chiew, Y, Chou, A, Cingarlini, S, Cloonan, N, Corbo, V, Davi, M, Duthie, F, Gill, A, Graham, J, Harliwong, I, Jamieson, N, Johns, A, Kench, J, Landoni, L, Lawlor, R, Mafficini, A, Merrett, N, Miotto, M, Musgrove, E, Nagrial, A, Oien, K, Pajic, M, Pinese, M, Robertson, A, Rooman, I, Rusev, B, Samra, J, Scardoni, M, Scarlett, C, Scarpa, A, Sereni, E, Sikora, K, Simbolo, M, Taschuk, M, Toon, C, Vicentini, C, Wu, J, Zeps, N, Behren, A, Burke, H, Cebon, J, Dagg, R, De Paoli-Iseppi, R, Dutton-Regester, K, Field, M, Fitzgerald, A, Hersey, P, Jakrot, V, Johansson, P, Kakavand, H, Kefford, R, Lau, L, Long, G, Pickett, H, Pritchard, A, Pupo, G, Saw, R, Schramm, S, Shang, C, Shang, P, Spillane, A, Stretch, J, Tembe, V, Thompson, J, Vilain, R, Wilmott, J, Yang, J, Hayward, N, Mann, G, Scolyer, R, Bartlett, J, Bavi, P, Chadwick, D, Chan-Seng-Yue, M, Cleary, S, Connor, A, Czajka, K, Denroche, R, Dhani, N, Eagles, J, Gallinger, S, Grant, R, Hedley, D, Hollingsworth, M, Jang, G, Johns, J, Kalimuthu, S, Liang, S, Lungu, I, Luo, X, Mbabaali, F, Mcpherson, T, Miller, J, Moore, M, Notta, F, Pasternack, D, Petersen, G, Roehrl, M, Sam, M, Selander, I, Serra, S, Shahabi, S, Thayer, S, Timms, L, Wilson, G, Wilson, J, Wouters, B, Beck, T, Bhandari, V, Collins, C, Fleshner, N, Fox, N, Fraser, M, Heisler, L, Lalonde, E, Livingstone, J, Meng, A, Sabelnykova, V, Shiah, Y, Van der Kwast, T, Bristow, R, Ding, S, Fan, D, Li, L, Nie, Y, Xiao, X, Xing, R, Yang, S, Yu, Y, Zhou, Y, Banks, R, Bourque, G, Brennan, P, Letourneau, L, Riazalhosseini, Y, Scelo, G, Vasudev, N, Viksna, J, Lathrop, M, Tost, J, Ahn, S, Aparicio, S, Arnould, L, Aure, M, Bhosle, S, Birney, E, Borg, A, Boyault, S, Brinkman, A, Brock, J, Broeks, A, Borresen-Dale, A, Caldas, C, Chin, S, Davies, H, Desmedt, C, Dirix, L, Dronov, S, Ehinger, A, Eyfjord, J, Fatima, A, Foekens, J, Futreal, P, Garred, O, Giri, D, Glodzik, D, Grabau, D, Hilmarsdottir, H, Hooijer, G, Jacquemier, J, Jang, S, Jonasson, J, Jonkers, J, King, T, Knappskog, S, Kong, G, Krishnamurthy, S, Lakhani, S, Langerod, A, Larsimont, D, Lee, H, Lee, M, Lingjaerde, O, Macgrogan, G, Martens, J, O'Meara, S, Pauporte, I, Pinder, S, Pivot, X, Provenzano, E, Purdie, C, Ramakrishna, M, Ramakrishnan, K, Reis-Filho, J, Richardson, A, Ringner, M, Rodriguez, J, Rodriguez-Gonzalez, F, Romieu, G, Salgado, R, Sauer, T, Shepherd, R, Sieuwerts, A, Simpson, P, Smid, M, Sotiriou, C, Span, P, Stefansson, O, Stenhouse, A, Stunnenberg, H, Sweep, F, Tan, B, Thomas, G, Thompson, A, Tommasi, S, Treilleux, I, Tutt, A, Ueno, N, Van Laere, S, Van den Eynden, G, Vermeulen, P, Viari, A, Vincent-Salomon, A, Wong, B, Yates, L, Zou, X, van Deurzen, C, van de Vijver, M, van't Veer, L, Ammerpohl, O, Aukema, S, Bergmann, A, Bernhart, S, Borkhardt, A, Borst, C, Burkhardt, B, Claviez, A, Goebler, M, Haake, A, Haas, S, Hansmann, M, Hoell, J, Hummel, M, Karsch, D, Klapper, W, Kneba, M, Kreuz, M, Kube, D, Kuppers, R, Lenze, D, Loeffler, M, Lopez, C, Mantovani-Loffler, L, Moller, P, Ott, G, Radlwimmer, B, Richter, J, Rohde, M, Rosenstiel, P, Rosenwald, A, Schilhabel, M, Schreiber, S, Stadler, P, Staib, P, Stilgenbauer, S, Sungalee, S, Szczepanowski, M, Toprak, U, Trumper, L, Wagener, R, Zenz, T, Hovestadt, V, von Kalle, C, Kool, M, Korshunov, A, Landgraf, P, Lehrach, H, Northcott, P, Pfister, S, Reifenberger, G, Warnatz, H, Wolf, S, Yaspo, M, Assenov, Y, Gerhauser, C, Minner, S, Schlomm, T, Simon, R, Sauter, G, Sultmann, H, Biswas, N, Maitra, A, Majumder, P, Sarin, R, Barbi, S, Bonizzato, G, Cantu, C, Dei Tos, A, Fassan, M, Grimaldi, S, Luchini, C, Malleo, G, Marchegiani, G, Milella, M, Paiella, S, Pea, A, Pederzoli, P, Ruzzenente, A, Salvia, R, Sperandio, N, Arai, Y, Hama, N, Hiraoka, N, Hosoda, F, Nakamura, H, Ojima, H, Okusaka, T, Totoki, Y, Urushidate, T, Fukayama, M, Ishikawa, S, Katai, H, Katoh, H, Komura, D, Rokutan, H, Saito-Adachi, M, Suzuki, A, Taniguchi, H, Tatsuno, K, Ushiku, T, Yachida, S, Yamamoto, S, Aikata, H, Arihiro, K, Ariizumi, S, Chayama, K, Furuta, M, Gotoh, K, Hayami, S, Hirano, S, Kawakami, Y, Maejima, K, Nakamura, T, Nakano, K, Ohdan, H, Sasaki-Oku, A, Tanaka, H, Ueno, M, Yamamoto, M, Yamaue, H, Choo, S, Cutcutache, I, Khuntikeo, N, Ong, C, Pairojkul, C, Popescu, I, Ahn, K, Aymerich, M, Lopez-Guillermo, A, Lopez-Otin, C, Puente, X, Campo, E, Amary, F, Baumhoer, D, Behjati, S, Bjerkehagen, B, Myklebost, O, Pillay, N, Tarpey, P, Tirabosco, R, Zaikova, O, Flanagan, A, Boultwood, J, Bowen, D, Cazzola, M, Green, A, Hellstrom-Lindberg, E, Malcovati, L, Nangalia, J, Papaemmanuil, E, Vyas, P, Ang, Y, Barr, H, Beardsmore, D, Eldridge, M, Gossage, J, Grehan, N, Hanna, G, Hayes, S, Hupp, T, Khoo, D, Lagergren, J, Lovat, L, Macrae, S, O'Donovan, M, O'Neill, J, Parsons, S, Preston, S, Puig, S, Roques, T, Sanders, G, Sothi, S, Tavare, S, Tucker, O, Turkington, R, Underwood, T, Welch, I, Fitzgerald, R, Berney, D, De Bono, J, Cahill, D, Camacho, N, Dennis, N, Dudderidge, T, Edwards, S, Fisher, C, Foster, C, Ghori, M, Gill, P, Gnanapragasam, V, Gundem, G, Hamdy, F, Hawkins, S, Hazell, S, Howat, W, Isaacs, W, Karaszi, K, Kay, J, Khoo, V, Kote-Jarai, Z, Kremeyer, B, Kumar, P, Lambert, A, Leongamornlert, D, Livni, N, Luxton, H, Marsden, L, Massie, C, Matthews, L, Mayer, E, Mcdermott, U, Merson, S, Neal, D, Nicol, D, Ogden, C, Rowe, E, Shah, N, Thomas, S, Verrill, C, Visakorpi, T, Warren, A, Whitaker, H, Zhang, H, van As, N, Eeles, R, Abeshouse, A, Agrawal, N, Akbani, R, Al-Ahmadie, H, Albert, M, Aldape, K, Ally, A, Appelbaum, E, Armenia, J, Asa, S, Auman, J, Balasundaram, M, Balu, S, Barnholtz-Sloan, J, Bathe, O, Baylin, S, Benz, C, Berchuck, A, Berrios, M, Bigner, D, Birrer, M, Bodenheimer, T, Boice, L, Bootwalla, M, Bosenberg, M, Bowlby, R, Boyd, J, Broaddus, R, Brock, M, Brooks, D, Bullman, S, Caesar-Johnson, S, Carey, T, Carlsen, R, Cerfolio, R, Chandan, V, Chen, H, Cherniack, A, Chien, J, Cho, J, Chuah, E, Cibulskis, C, Cope, L, Cordes, M, Curley, E, Czerniak, B, Danilova, L, Davis, I, Defreitas, T, Demchok, J, Dhalla, N, Dhir, R, Doddapaneni, H, El-Naggar, A, Felau, I, Ferguson, M, Finocchiaro, G, Fong, K, Frazer, S, Friedman, W, Fronick, C, Fulton, L, Gabriel, S, Gao, J, Gehlenborg, N, Gershenwald, J, Ghossein, R, Giama, N, Gibbs, R, Gomez, C, Govindan, R, Hayes, D, Hegde, A, Heiman, D, Heins, Z, Hepperla, A, Holbrook, A, Holt, R, Hoyle, A, Hruban, R, Hu, J, Huntsman, D, Huse, J, Iacobuzio-Donahue, C, Ittmann, M, Jayaseelan, J, Jefferys, S, Jones, C, Jones, S, Juhl, H, Kang, K, Karlan, B, Kasaian, K, Kebebew, E, Korchina, V, Kundra, R, Lai, P, Lander, E, Le, X, Levine, D, Lewis, L, Ley, T, Li, H, Lin, P, Linehan, W, Lype, L, Ma, Y, Maglinte, D, Mardis, E, Marks, J, Marra, M, Matthew, T, Mayo, M, Mccune, K, Meier, S, Meng, S, Mieczkowski, P, Mikkelsen, T, Miller, C, Mills, G, Moore, R, Morrison, C, Mose, L, Moser, C, Mungall, A, Mungall, K, Mutch, D, Muzny, D, Myers, J, Newton, Y, Noble, M, O'Donnell, P, O'Neill, B, Ochoa, A, Parker, J, Pass, H, Pastore, A, Pennell, N, Perou, C, Petrelli, N, Potapova, O, Rader, J, Ramalingam, S, Rathmell, W, Reuter, V, Reynolds, S, Ringel, M, Roach, J, Roberts, L, Sadeghi, S, Saller, C, Sanchez-Vega, F, Schadendorf, D, Schein, J, Schmidt, H, Schultz, N, Seethala, R, Senbabaoglu, Y, Shelton, T, Shi, Y, Shih, J, Shmulevich, I, Shriver, C, Signoretti, S, Simons, J, Singer, S, Sipahimalani, P, Skelly, T, Smith-McCune, K, Socci, N, Soloway, M, Sood, A, Tam, A, Tan, D, Tarnuzzer, R, Thiessen, N, Thompson, R, Thorne, L, Tsao, M, Umbricht, C, Van Den Berg, D, Van Meir, E, Veluvolu, U, Voet, D, Wang, L, Weinberger, P, Weisenberger, D, Wigle, D, Wilkerson, M, Wilson, R, Winterhoff, B, Wiznerowicz, M, Wong, T, Wong, W, Xi, L, Yau, C, Consortium, ICGC/TCGA Pan-Cancer Analysis of Whole Genomes, Demeulemeester, Jonas, Desmedt, Christine, Van Loo, Peter, Barcelona Supercomputing Center, Imperial College Healthcare NHS Trust- BRC Funding, Cancer Research UK, Basic (bio-) Medical Sciences, and Laboratory for Medical and Molecular Oncology

Subjects
Male, tert promoter mutations, Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2], DNA Mutational Analysis, Normal tissue, systematic analysis, Germline, Transcriptome, 0302 clinical medicine, Aetiology, Càncer, Cellular Senescence, Cancer, 0303 health sciences, dna-damage, Massive parallel sequencing, Pan cancer, REARRANGEMENTS, High-Throughput Nucleotide Sequencing, Genomics, Sciences bio-médicales et agricoles, Telomere, COMPREHENSIVE, 3. Good health, TERT PROMOTER MUTATIONS, signatures, 030220 oncology & carcinogenesis, Science & Technology - Other Topics, Erfðarannsóknir, Human, Informàtica::Aplicacions de la informàtica::Bioinformàtica [Àrees temàtiques de la UPC], Evolution, RNA Splicing, Article, Evolution, Molecular, Structural variation, RC0254, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Genetic, genomics, SYSTEMATIC ANALYSIS, Genetics, Genomics--Databases, Humans, Genetic Testing, Molecular Biology, SIGNATURES, Whole genome sequencing, 1000 Multidisciplinary, Chromothripsis, Science & Technology, RC0254 Neoplasms. Tumors. Oncology (including Cancer), Information Dissemination, ResearchInstitutes_Networks_Beacons/mcrc, Prevention, Biology and Life Sciences, Molecular, Oncogenes, Cloud Computing, medicine.disease, Genòmica, Compute clouds, Mutation, 570 Life sciences, biology, COMPREHENSIVE CHARACTERIZATION, Genètica, Whole Genome Sequencing--methods, Background information, Genetic / genetics, Genome, Germ-Line Mutation / genetics, Human / genetics, ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium, Medizin, Whole-genome, Genome mapping, Neoplasms, 2.1 Biological and endogenous factors, Promoter Regions, Genetic, Càncer -- Aspectes genètics, Telomerase, Women's cancers Radboud Institute for Molecular Life Sciences [Radboudumc 17], Multidisciplinary, Manchester Cancer Research Centre, genomics, cancer, profiling, 3rd-DAS, 10124 Institute of Molecular Life Sciences, Women's cancers Radboud Institute for Health Sciences [Radboudumc 17], Multidisciplinary Sciences, Parallel sequencing, Female, profiling, Medical Genetics, Engineering sciences. Technology, Biotechnology, General Science & Technology, The Cancer Genome Atlas, 610 Medicine & health, Computational biology, QH426 Genetics, Biology, Consortium of the International Cancer Genome Consortium, Promoter Regions, Germline mutation, Pan-cancer analysis, Krabbameinsrannsóknir, medicine, cancer, ddc:610, QH426, Germ-Line Mutation, Medicinsk genetik, Krabbamein, 030304 developmental biology, Cell Proliferation, LANDSCAPE, Genome, Human, comprehensive characterization, Pan-cancer analysis of whole genomes, Point mutation, Human Genome, Reproducibility of Results, SOMATIC MUTATIONS, EVOLUTION, Cancer, sequencing, Chromothripsis, telomere, DNA-DAMAGE, Mutagenesis, PATTERNS, 3111 Biomedicine, CHARACTERIZATION
Abstract

Publisher's version (útgefin grein), Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1,2,3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10,11,12,13,14,15,16,17,18., Competing interests Gad Getz receives research funds from IBM and Pharmacyclics and is an inventor on patent applications related to MuTect, ABSOLUTE, MutSig, MSMuTect, MSMutSig and POLYSOLVER. Hikmat Al-Ahmadie is consultant for AstraZeneca and Bristol-Myers Squibb. Samuel Aparicio is a founder and shareholder of Contextual Genomics. Pratiti Bandopadhayay receives grant funding from Novartis for an unrelated project. Rameen Beroukhim owns equity in Ampressa Therapeutics. Andrew Biankin receives grant funding from Celgene, AstraZeneca and is a consultant for or on advisory boards of AstraZeneca, Celgene, Elstar Therapeutics, Clovis Oncology and Roche. Ewan Birney is a consultant for Oxford Nanopore, Dovetail and GSK. Marcus Bosenberg is a consultant for Eli Lilly. Atul Butte is a cofounder of and consultant for Personalis, NuMedii, a consultant for Samsung, Geisinger Health, Mango Tree Corporation, Regenstrief Institute and in the recent past a consultant for 10x Genomics and Helix, a shareholder in Personalis, a minor shareholder in Apple, Twitter, Facebook, Google, Microsoft, Sarepta, 10x Genomics, Amazon, Biogen, CVS, Illumina, Snap and Sutro and has received honoraria and travel reimbursement for invited talks from Genentech, Roche, Pfizer, Optum, AbbVie and many academic institutions and health systems. Carlos Caldas has served on the Scientific Advisory Board of Illumina. Lorraine Chantrill acted on an advisory board for AMGEN Australia in the past 2 years. Andrew D. Cherniack receives research funding from Bayer. Helen Davies is an inventor on a number of patent applications that encompass the use of mutational signatures. Francisco De La Vega was employed at Annai Systems during part of the project. Ronny Drapkin serves on the scientific advisory board of Repare Therapeutics and Siamab Therapeutics. Rosalind Eeles has received an honorarium for the GU-ASCO meeting in San Francisco in January 2016 as a speaker, a honorarium and support from Janssen for the RMH FR meeting in November 2017 as a speaker (title: genetics and prostate cancer), a honorarium for an University of Chicago invited talk in May 2018 as speaker and an educational honorarium paid by Bayer & Ipsen to attend GU Connect ‘Treatment sequencing for mCRPC patients within the changing landscape of mHSPC’ at a venue at ESMO, Barcelona, on 28 September 2019. Paul Flicek is a member of the scientific advisory boards of Fabric Genomics and Eagle Genomics. Ronald Ghossein is a consultant for Veracyte. Dominik Glodzik is an inventor on a number of patent applications that encompass the use of mutational signatures. Eoghan Harrington is a full-time employee of Oxford Nanopore Technologies and is a stock holder. Yann Joly is responsible for the Data Access Compliance Office (DACO) of ICGC 2009-2018. Sissel Juul is a full-time employee of Oxford Nanopore Technologies and is a stock holder. Vincent Khoo has received personal fees and non-financial support from Accuray, Astellas, Bayer, Boston Scientific and Janssen. Stian Knappskog is a coprincipal investigator on a clinical trial that receives research funding from AstraZeneca and Pfizer. Ignaty Leshchiner is a consultant for PACT Pharma. Carlos López-Otín has ownership interest (including stock and patents) in DREAMgenics. Matthew Meyerson is a scientific advisory board chair of, and consultant for, OrigiMed, has obtained research funding from Bayer and Ono Pharma and receives patent royalties from LabCorp. Serena Nik-Zainal is an inventor on a number of patent applications that encompass the use of mutational signatures. Nathan Pennell has done consulting work with Merck, Astrazeneca, Eli Lilly and Bristol-Myers Squibb. Xose S. Puente has ownership interest (including stock and patents in DREAMgenics. Benjamin J. Raphael is a consultant for and has ownership interest (including stock and patents) in Medley Genomics. Jorge Reis-Filho is a consultant for Goldman Sachs and REPARE Therapeutics, member of the scientific advisory board of Volition RX and Paige.AI and an ad hoc member of the scientific advisory board of Ventana Medical Systems, Roche Tissue Diagnostics, InVicro, Roche, Genentech and Novartis. Lewis R. Roberts has received grant support from ARIAD Pharmaceuticals, Bayer, BTG International, Exact Sciences, Gilead Sciences, Glycotest, RedHill Biopharma, Target PharmaSolutions and Wako Diagnostics and has provided advisory services to Bayer, Exact Sciences, Gilead Sciences, GRAIL, QED Therapeutics and TAVEC Pharmaceuticals. Richard A. Scolyer has received fees for professional services from Merck Sharp & Dohme, GlaxoSmithKline Australia, Bristol-Myers Squibb, Dermpedia, Novartis Pharmaceuticals Australia, Myriad, NeraCare GmbH and Amgen. Tal Shmaya is employed at Annai Systems. Reiner Siebert has received speaker honoraria from Roche and AstraZeneca. Sabina Signoretti is a consultant for Bristol-Myers Squibb, AstraZeneca, Merck, AACR and NCI and has received funding from Bristol-Myers Squibb, AstraZeneca, Exelixis and royalties from Biogenex. Jared Simpson has received research funding and travel support from Oxford Nanopore Technologies. Anil K. Sood is a consultant for Merck and Kiyatec, has received research funding from M-Trap and is a shareholder in BioPath. Simon Tavaré is on the scientific advisory board of Ipsen and a consultant for Kallyope. John F. Thompson has received honoraria and travel support for attending advisory board meetings of GlaxoSmithKline and Provectus and has received honoraria for participation in advisory boards for MSD Australia and BMS Australia. Daniel Turner is a full-time employee of Oxford Nanopore Technologies and is a stock holder. Naveen Vasudev has received speaker honoraria and/or consultancy fees from Bristol-Myers Squibb, Pfizer, EUSA pharma, MSD and Novartis. Jeremiah A. Wala is a consultant for Nference. Daniel J. Weisenberger is a consultant for Zymo Research. Dai-Ying Wu is employed at Annai Systems. Cheng-Zhong Zhang is a cofounder and equity holder of Pillar Biosciences, a for-profit company that specializes in the development of targeted sequencing assays. The other authors declare no competing interests.

Published
2020
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