Analyses of non-coding somatic drivers in 2,658 cancer whole genomes

Autor: Rheinbay E., Nielsen M. M., Abascal F., Wala J. A., Shapira O., Tiao G., Hornshoj H., Hess J. M., Juul R. I., Lin Z., Feuerbach L., Sabarinathan R., Madsen T., Kim J., Mularoni L., Shuai S., Lanzos A., Herrmann C., Maruvka Y. E., Shen C., Amin S. B., Bandopadhayay P., Bertl J., Boroevich K. A., Busanovich J., Carlevaro-Fita J., Chakravarty D., Chan C. W. Y., Craft D., Dhingra P., Diamanti K., Fonseca N. A., Gonzalez-Perez A., Guo Q., Hamilton M. P., Haradhvala N. J., Hong C., Isaev K., Johnson T. A., Juul M., Kahles A., Kahraman A., Kim Y., Komorowski J., Kumar K., Kumar S., Lee D., Lehmann K. -V., Li Y., Liu E. M., Lochovsky L., Park K., Pich O., Roberts N. D., Saksena G., Schumacher S. E., Sidiropoulos N., Sieverling L., Sinnott-Armstrong N., Stewart C., Tamborero D., Tubio J. M. C., Umer H. M., Uuskula-Reimand L., Wadelius C., Wadi L., Yao X., Zhang C. -Z., Zhang J., Haber J. E., Hobolth A., Imielinski M., Kellis M., Lawrence M. S., von Mering C., Nakagawa H., Raphael B. J., Rubin M. A., Sander C., Stein L. D., Stuart J. M., Tsunoda T., Wheeler D. A., Johnson R., Reimand J., Gerstein M., Khurana E., Campbell P. J., Lopez-Bigas N., Bader G. D., Barenboim J., Beroukhim R., Brunak S., Chen K., Choi J. K., Deu-Pons J., Fink J. L., Frigola J., Gambacorti Passerini C., Garsed D. W., Getz G., Gut I. G., Haan D., Harmanci A. O., Helmy M., Hodzic E., Izarzugaza J. M. G., Kim J. K., Korbel J. O., Larsson E., Li S., Li X., Lou S., Marchal K., Martincorena I., Martinez-Fundichely A., McGillivray P. D., Meyerson W., Muinos F., Paczkowska M., Pedersen J. S., Pons T., Pulido-Tamayo S., Reyes-Salazar I., Reyna M. A., Rubio-Perez C., Sahinalp S. C., Salichos L., Shackleton M., Shrestha R., Valencia A., Vazquez M., Verbeke L. P. C., Wang J., Warrell J., Waszak S. M., Weischenfeldt J., Wu G., Yu J., Zhang X., Zhang Y., Zhao Z., Zou L., Akdemir K. C., Alvarez E. G., Baez-Ortega A., Boutros P. C., Bowtell D. D. L., Brors B., Burns K. H., Chan K., Cortes-Ciriano I., Dueso-Barroso A., Dunford A. J., Edwards P. A., Estivill X., Etemadmoghadam D., Frenkel-Morgenstern M., Gordenin D. A., Hutter B., Jones D. T. W., Ju Y. S., Kazanov M. D., Klimczak L. J., Koh Y., Lee E. A., Lee J. J. -K., Lynch A. G., Macintyre G., Markowetz F., Meyerson M., Miyano S., Navarro F. C. P., Ossowski S., Park P. J., Pearson J. V., Puiggros M., Rippe K., Roberts S. A., Rodriguez-Martin B., Scully R., Torrents D., Villasante I., Waddell N., Yang L., Yoon S. -S., Zamora J.
Přispěvatelé: Rheinbay, E, Nielsen, M, Abascal, F, Wala, J, Shapira, O, Tiao, G, Hornshoj, H, Hess, J, Juul, R, Lin, Z, Feuerbach, L, Sabarinathan, R, Madsen, T, Kim, J, Mularoni, L, Shuai, S, Lanzos, A, Herrmann, C, Maruvka, Y, Shen, C, Amin, S, Bandopadhayay, P, Bertl, J, Boroevich, K, Busanovich, J, Carlevaro-Fita, J, Chakravarty, D, Chan, C, Craft, D, Dhingra, P, Diamanti, K, Fonseca, N, Gonzalez-Perez, A, Guo, Q, Hamilton, M, Haradhvala, N, Hong, C, Isaev, K, Johnson, T, Juul, M, Kahles, A, Kahraman, A, Kim, Y, Komorowski, J, Kumar, K, Kumar, S, Lee, D, Lehmann, K, Li, Y, Liu, E, Lochovsky, L, Park, K, Pich, O, Roberts, N, Saksena, G, Schumacher, S, Sidiropoulos, N, Sieverling, L, Sinnott-Armstrong, N, Stewart, C, Tamborero, D, Tubio, J, Umer, H, Uuskula-Reimand, L, Wadelius, C, Wadi, L, Yao, X, Zhang, C, Zhang, J, Haber, J, Hobolth, A, Imielinski, M, Kellis, M, Lawrence, M, von Mering, C, Nakagawa, H, Raphael, B, Rubin, M, Sander, C, Stein, L, Stuart, J, Tsunoda, T, Wheeler, D, Johnson, R, Reimand, J, Gerstein, M, Khurana, E, Campbell, P, Lopez-Bigas, N, Bader, G, Barenboim, J, Beroukhim, R, Brunak, S, Chen, K, Choi, J, Deu-Pons, J, Fink, J, Frigola, J, Gambacorti Passerini, C, Garsed, D, Getz, G, Gut, I, Haan, D, Harmanci, A, Helmy, M, Hodzic, E, Izarzugaza, J, Korbel, J, Larsson, E, Li, S, Li, X, Lou, S, Marchal, K, Martincorena, I, Martinez-Fundichely, A, Mcgillivray, P, Meyerson, W, Muinos, F, Paczkowska, M, Pedersen, J, Pons, T, Pulido-Tamayo, S, Reyes-Salazar, I, Reyna, M, Rubio-Perez, C, Sahinalp, S, Salichos, L, Shackleton, M, Shrestha, R, Valencia, A, Vazquez, M, Verbeke, L, Wang, J, Warrell, J, Waszak, S, Weischenfeldt, J, Wu, G, Yu, J, Zhang, X, Zhang, Y, Zhao, Z, Zou, L, Akdemir, K, Alvarez, E, Baez-Ortega, A, Boutros, P, Bowtell, D, Brors, B, Burns, K, Chan, K, Cortes-Ciriano, I, Dueso-Barroso, A, Dunford, A, Edwards, P, Estivill, X, Etemadmoghadam, D, Frenkel-Morgenstern, M, Gordenin, D, Hutter, B, Jones, D, Ju, Y, Kazanov, M, Klimczak, L, Koh, Y, Lee, E, Lee, J, Lynch, A, Macintyre, G, Markowetz, F, Meyerson, M, Miyano, S, Navarro, F, Ossowski, S, Park, P, Pearson, J, Puiggros, M, Rippe, K, Roberts, S, Rodriguez-Martin, B, Scully, R, Torrents, D, Villasante, I, Waddell, N, Yang, L, Yoon, S, Zamora, J, Gonzalez-Perez, Abel [0000-0002-8582-4660], Apollo - University of Cambridge Repository, 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
Jazyk: angličtina
Rok vydání: 2020
Předmět:
QA75
EXPRESSION
SELECTION
Untranslated region
medicine.medical_specialty
GENES
QA75 Electronic computers. Computer science
610 Medicine & health
Genome-wide association study
Tumors -- Genètica
Computational biology
Biology
Genoma humà
ANNOTATION
Genome
Article
RC0254
03 medical and health sciences
0302 clinical medicine
SDG 3 - Good Health and Well-being
REGULATORY MUTATIONS
Cancer genomics
Medicine and Health Sciences
medicine
RECURRENT
Gene
030304 developmental biology
Medicinsk genetik
0303 health sciences
Women's cancers Radboud Institute for Molecular Life Sciences [Radboudumc 17]
Multidisciplinary
LANDSCAPE
RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Point mutation
Mutació (Biologia)
Biology and Life Sciences
Cancer genomics
Computational biology
bioinformatics
protein-coding genes
cancer
non-coding
3rd-DAS
Human genetics
Women's cancers Radboud Institute for Health Sciences [Radboudumc 17]
Computational biology and bioinformatics
3. Good health
TERT PROMOTER MUTATIONS
TARGET
DISCOVERY
Medical genetics
Human genome
Medical Genetics
030217 neurology & neurosurgery
Zdroj: Rheinbay, E, Nielsen, M M, Abascal, F, Wala, J A, Shapira, O, Tiao, G, Hornshøj, H, Hess, J M, Juul, R I, Lin, Z, Feuerbach, L, Sabarinathan, R, Madsen, T, Kim, J, Mularoni, L, Shuai, S, Lanzós, A, Herrmann, C, Maruvka, Y E, Shen, C, Amin, S B, Bandopadhayay, P, Bertl, J, Boroevich, K A, Busanovich, J, Carlevaro-Fita, J, Chakravarty, D, Chan, C W Y, Craft, D, Dhingra, P, Diamanti, K, Fonseca, N A, Gonzalez-Perez, A, Guo, Q, Hamilton, M P, Haradhvala, N J, Hong, C, Zhang, C Z, Hobolth, A, Pedersen, J S & PCAWG Consortium 2020, ' Analyses of non-coding somatic drivers in 2,658 cancer whole genomes ', Nature, vol. 578, no. 7793, pp. 102-111 . https://doi.org/10.1038/s41586-020-1965-x
Rheinbay, E, Nielsen, M M, Abascal, F, Wala, J A, Shapira, O, Tiao, G, Hornshøj, H, Hess, J M, Juul, R I, Lin, Z, Feuerbach, L, Sabarinathan, R, Madsen, T, Kim, J, Mularoni, L, Shuai, S, Lanzós, A, Herrmann, C, Maruvka, Y E, Shen, C, Amin, S B, Bandopadhayay, P, Bertl, J, Boroevich, K A, Busanovich, J, Carlevaro-Fita, J, Chakravarty, D, Chan, C W Y, Craft, D, Dhingra, P, Diamanti, K, Fonseca, N A, Gonzalez-Perez, A, Guo, Q, Hamilton, M P, Haradhvala, N J, Hong, C, Isaev, K, Johnson, T A, Juul, M, Kahles, A, Kahraman, A, Kim, Y, Komorowski, J, Kumar, K, Kumar, S, Lee, D, Sidiropoulos, N, Weischenfeldt, J, Pedersen, J S & PCAWG Drivers and Functional Interpretation Working Group 2020, ' Analyses of non-coding somatic drivers in 2,658 cancer whole genomes ', Nature, vol. 578, no. 7793, pp. 102-111 . https://doi.org/10.1038/s41586-020-1965-x
NATURE
Nature, 578, 102-111
Nature
Rheinbay, Esther; Nielsen, Morten Muhlig; Abascal, Federico; Wala, Jeremiah A; Shapira, Ofer; Tiao, Grace; Hornshøj, Henrik; Hess, Julian M; Juul, Randi Istrup; Lin, Ziao; Feuerbach, Lars; Sabarinathan, Radhakrishnan; Madsen, Tobias; Kim, Jaegil; Mularoni, Loris; Shuai, Shimin; Lanzos, Andrés; Herrmann, Carl; Maruvka, Yosef E; Shen, Ciyue; ... (2020). Analyses of non-coding somatic drivers in 2,658 cancer whole genomes. Nature, 578(7793), pp. 102-111. Springer Nature 10.1038/s41586-020-1965-x
Nature, 578, 7793, pp. 102-111
PCAWG Drivers and Functional Interpretation Working Group, PCAWG Structural Variation Working Group & PCAWG Consortium 2020, ' Analyses of non-coding somatic drivers in 2,658 cancer whole genomes ', Nature, vol. 578, no. 7793, pp. 102-111 . https://doi.org/10.1038/s41586-020-1965-x
ISSN: 0028-0836
1476-4687
Popis: The discovery of drivers of cancer has traditionally focused on protein-coding genes1–4. Here we present analyses of driver point mutations and structural variants in non-coding regions across 2,658 genomes from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium5 of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). For point mutations, we developed a statistically rigorous strategy for combining significance levels from multiple methods of driver discovery that overcomes the limitations of individual methods. For structural variants, we present two methods of driver discovery, and identify regions that are significantly affected by recurrent breakpoints and recurrent somatic juxtapositions. Our analyses confirm previously reported drivers6,7, raise doubts about others and identify novel candidates, including point mutations in the 5′ region of TP53, in the 3′ untranslated regions of NFKBIZ and TOB1, focal deletions in BRD4 and rearrangements in the loci of AKR1C genes. We show that although point mutations and structural variants that drive cancer are less frequent in non-coding genes and regulatory sequences than in protein-coding genes, additional examples of these drivers will be found as more cancer genomes become available.
Analyses of 2,658 whole genomes across 38 types of cancer identify the contribution of non-coding point mutations and structural variants to driving cancer.
Databáze: OpenAIRE
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