Integrated genomic characterization of pancreatic ductal adenocarcinoma

Raphael, B. J. et al. (2017) Integrated genomic characterization of pancreatic ductal adenocarcinoma. Cancer Cell, 32(2), 185-203.e13. (doi:10.1016/j.ccell.2017.07.007) (PMID:28810144)

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Abstract

We performed integrated genomic, transcriptomic, and proteomic profiling of 150 pancreatic ductal adenocarcinoma (PDAC) specimens, including samples with characteristic low neoplastic cellularity. Deep whole-exome sequencing revealed recurrent somatic mutations in KRAS, TP53, CDKN2A, SMAD4, RNF43, ARID1A, TGFβR2, GNAS, RREB1, and PBRM1. KRAS wild-type tumors harbored alterations in other oncogenic drivers, including GNAS, BRAF, CTNNB1, and additional RAS pathway genes. A subset of tumors harbored multiple KRAS mutations, with some showing evidence of biallelic mutations. Protein profiling identified a favorable prognosis subset with low epithelial-mesenchymal transition and high MTOR pathway scores. Associations of non-coding RNAs with tumor-specific mRNA subtypes were also identified. Our integrated multi-platform analysis reveals a complex molecular landscape of PDAC and provides a roadmap for precision medicine.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Bailey, Dr Peter and Biankin, Professor Andrew and Chang, Dr David
Authors: Raphael, B. J., Hruban, R. H., Aguirre, A. J., Moffitt, R. A., Yeh, J. J., Stewart, C., Robertson, A. G., Cherniack, A. D., Gupta, M., Getz, G., Gabriel, S. B., Meyerson, M., Cibulskis, C., Fei, S. S., Hinoue, T., Shen, H., Laird, P. W., Ling, S., Lu, Y., Mills, G. B., Akbani, R., Loher, P., Londin, E. R., Rigoutsos, I., Telonis, A. G., Gibb, E. A., Goldenberg, A., Mezlini, A. M., Hoadley, K. A., Collisson, E., Lander, E., Murray, B. A., Hess, J., Rosenberg, M., Bergelson, L., Zhang, H., Cho, J., Tiao, G., Kim, J., Livitz, D., Leshchiner, I., Reardon, B., Van Allen, E., Kamburov, A., Beroukhim, R., Saksena, G., Schumacher, S. E., Noble, M. S., Heiman, D. I., Gehlenborg, N., Kim, J., Lawrence, M. S., Adsay, V., Petersen, G., Klimstra, D., Bardeesy, N., Leiserson, M. D.M., Bowlby, R., Kasaian, K., Birol, I., Mungall, K. L., Sadeghi, S., Weinstein, J. N., Spellman, P. T., Liu, Y., Amundadottir, L. T., Tepper, J., Singhi, A. D., Dhir, R., Paul, D., Smyrk, T., Zhang, L., Kim, P., Bowen, J., Frick, J., Gastier-Foster, J. M., Gerken, M., Lau, K., Leraas, K. M., Lichtenberg, T. M., Ramirez, N. C., Renkel, J., Sherman, M., Wise, L., Yena, P., Zmuda, E., Shih, J., Ally, A., Balasundaram, M., Carlsen, R., Chu, A., Chuah, E., Clarke, A., Dhalla, N., Holt, R. A., Jones, S. J.M., Lee, D., Ma, Y., Marra, M. A., Mayo, M., Moore, R. A., Mungall, A. J., Schein, J. E., Sipahimalani, P., Tam, A., Thiessen, N., Tse, K., Wong, T., Brooks, D., Auman, J. T., Balu, S., Bodenheimer, T., Hayes, D. N., Hoyle, A. P., Jefferys, S. R., Jones, C. D., Meng, S., Mieczkowski, P. A., Mose, L. E., Perou, C. M., Perou, A. H., Roach, J., Shi, Y., Simons, J. V., Skelly, T., Soloway, M. G., Tan, D., Veluvolu, U., Parker, J. S., Wilkerson, M. D., Korkut, A., Senbabaoglu, Y., Burch, P., McWilliams, R., Chaffee, K., Oberg, A., Zhang, W., Gingras, M.-C., Wheeler, D. A., Xi, L., Albert, M., Bartlett, J., Sekhon, H., Stephen, Y., Howard, Z., Judy, M., Breggia, A., Shroff, R. T., Chudamani, S., Liu, J., Lolla, L., Naresh, R., Pihl, T., Sun, Q., Wan, Y., Wu, Y., Jennifer, S., Roggin, K., Becker, K.-F., Behera, M., Bennett, J., Boice, L., Burks, E., Carlotti Junior, C. G., Chabot, J., Pretti da Cunha Tirapelli, D., Sebastião dos Santos, J., Dubina, M., Eschbacher, J., Huang, M., Huelsenbeck-Dill, L., Jenkins, R., Karpov, A., Kemp, R., Lyadov, V., Maithel, S., Manikhas, G., Montgomery, E., Noushmehr, H., Osunkoya, A., Owonikoko, T., Paklina, O., Potapova, O., Ramalingam, S., Rathmell, W. K., Rieger-Christ, K., Saller, C., Setdikova, G., Shabunin, A., Sica, G., Su, T., Sullivan, T., Swanson, P., Tarvin, K., Tavobilov, M., Thorne, L. B., Urbanski, S., Voronina, O., Wang, T., Crain, D., Curley, E., Gardner, J., Mallery, D., Morris, S., Paulauskis, J., Penny, R., Shelton, C., Shelton, T., Janssen, K.-P., Bathe, O., Bahary, N., Slotta-Huspenina, J., Johns, A., Hibshoosh, H., Hwang, R. F., Sepulveda, A., Radenbaugh, A., Baylin, S. B., Berrios, M., Bootwalla, M. S., Holbrook, A., Lai, P. H., Maglinte, D. T., Mahurkar, S., Triche, T. J., Van Den Berg, D. J., Weisenberger, D. J., Chin, L., Kucherlapati, R., Kucherlapati, M., Pantazi, A., Park, P., Saksena, G., Voet, D., Lin, P., Frazer, S., Defreitas, T., Meier, S., Chin, L., Kwon, S. Y., Kim, Y. H., Park, S.-J., Han, S.-S., Kim, S. H., Kim, H., Furth, E., Tempero, M., Sander, C., Biankin, A., Chang, D., Bailey, P., Gill, A., Kench, J., Grimmond, S., Johns, A., Cancer Genome Initiative (APGI, A. P., Postier, R., Zuna, R., Sicotte, H., Demchok, J. A., Ferguson, M. L., Hutter, C. M., Mills Shaw, K. R., Sheth, M., Sofia, H. J., Tarnuzzer, R., Wang, Z., Yang, L., Zhang, J. (J.), Felau, I., and Zenklusen, J. C.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Cancer Cell
Publisher:Elsevier (Cell Press)
ISSN:1535-6108
ISSN (Online):1878-3686
Published Online:14 August 2017
Copyright Holders:Copyright © 2017 The Authors
First Published:First published in Cancer Cell 32(2):185-203.e13
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
690421Glasgow Molecular Pathology (GMP) NodeKarin OienMedical Research Council (MRC)MR/N005813/1ICS - EXPERIMENTAL THERAPEUTICS