Evidence that synthetic lethality underlies the mutual exclusivity of oncogenic KRAS and EGFR mutations in lung adenocarcinoma

eLife

Volumn 4, Issue JUNE, 2015, Pages 1-23

  Unni, Arun M ^a   Lockwood, William W ^a,b   Zejnullahu, Kreshnik ^a   Lee Lin, Shih Queen ^a   Varmus, Harold ^a,c  

^a NATIONAL HUMAN GENOME RESEARCH INSTITUTE   (United States)

^b BRITISH COLUMBIA CANCER RESEARCH CENTRE   (Canada)

^c WEILL CORNELL MEDICAL COLLEGE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EPIDERMAL GROWTH FACTOR RECEPTOR; MITOGEN ACTIVATED PROTEIN KINASE; PHOSPHATIDYLINOSITOL 4, 5 BISPHOSPHATE 3 KINASE; PROTEIN KINASE LKB1; RAF PROTEIN; STRESS ACTIVATED PROTEIN KINASE; SYNAPTOPHYSIN; UNCLASSIFIED DRUG; EGFR PROTEIN, HUMAN; KRAS PROTEIN, HUMAN; MUTANT PROTEIN; PROTEIN P21;

ALLELIC EXCLUSION; ANIMAL MODEL; ANIMAL TISSUE; APOPTOSIS; ARTICLE; AUTOPHAGY; CARCINOGENESIS; CELL CYCLE; CELL STRUCTURE; CELL VACUOLE; CELL VIABILITY; CONTROLLED STUDY; CUTANEOUS MELANOMA; CYTOTOXICITY; DNA METHYLATION; EXOME; GENE DOSAGE; GENE EXPRESSION PROFILING; GENE FUNCTION; GENE INDUCTION; GENE MUTATION; GENETIC ASSOCIATION; GENOME ANALYSIS; HUMAN; HUMAN CELL; KRAS GENE; LUNG ADENOCARCINOMA; LUNG ALVEOLUS EPITHELIUM; MAJOR CLINICAL STUDY; MOUSE; NONHUMAN; ONCOGENE; PHENOTYPE; PINOCYTOSIS; PROTEIN ANALYSIS; PROTO ONCOGENE; RECOMBINANT PLASMID; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; SMOKING; WESTERN BLOTTING; ADENOCARCINOMA; ANIMAL; CELL SURVIVAL; DISEASE MODEL; GENETICS; LUNG TUMOR; METABOLISM; MUTATION; PATHOLOGY; TRANSGENIC MOUSE; TUMOR CELL LINE;

MUS MUSCULUS;

ADENOCARCINOMA; ANIMALS; CELL LINE, TUMOR; CELL SURVIVAL; DISEASE MODELS, ANIMAL; GENE EXPRESSION PROFILING; HUMANS; LUNG NEOPLASMS; MICE, TRANSGENIC; MUTANT PROTEINS; MUTATION; PROTO-ONCOGENE PROTEINS P21(RAS); RECEPTOR, EPIDERMAL GROWTH FACTOR;

EID: 84933039054     PISSN: None     EISSN: 2050084X     Source Type: Journal    
DOI: 10.7554/eLife.06907     Document Type: Article

References (52)

1. Ahronian LG, Sennott EM, Van Allen EM, Wagle N, Kwak EL, Faris JE, Godfrey JT, Nishimura K, Lynch KD, Mermel CH, Lockerman EL, Kalsy A, Gurski JM Jr, Bahl S, Anderka K, Green LM, Lennon NJ, Huynh TG, Mino-Kenudson M, Getz G, Dias-Santagata D, Iafrate AJ, Engelman JA, Garraway LA, Corcoran RB. 2015. Clinical acquired resistance to RAF inhibitor combinations in BRAF-mutant colorectal Cancer through MAPK pathway alterations. Cancer Discovery 5:358-367. doi: 10.1158/2159-8290.CD-14-1518.
2. Arao T, Fukumoto H, Takeda M, Tamura T, Saijo N, Nishio K. 2004. Small in-frame deletion in the epidermal growth factor receptor as a target for ZD6474. Cancer Research 64:9101-9104. doi: 10.1158/0008-5472.CAN-04-2360.
3. Bhanot H, Young AM, Overmeyer JH, Maltese WA. 2010. Induction of nonapoptotic cell death by activated Ras requires inverse regulation of Rac1 and Arf6. Molecular Cancer Research 8:1358-1374. doi: 10.1158/1541-7786. MCR-10-0090.
4. Cancer Genome Atlas Network. 2012. Comprehensive molecular characterization of human colon and rectal cancer. Nature 487:330-337. doi: 10.1038/nature11252.
5. Cancer Genome Atlas Research Network. 2008. Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature 455:1061-1068. doi: 10.1038/nature07385.
6. Cancer Genome Atlas Research Network. 2011. Integrated genomic analyses of ovarian carcinoma. Nature 474: 609-615. doi: 10.1038/nature10166.
7. Cancer Genome Atlas Research Network. 2013. Comprehensive molecular characterization of clear cell renal cell carcinoma. Nature 499:43-49. doi: 10.1038/nature12222.
8. Cancer Genome Atlas Research Network. 2014. Comprehensive molecular profiling of lung adenocarcinoma. Nature 511:543-550. doi: 10.1038/nature13385.
9. Cerami E, Gao J, Dogrusoz U, Gross BE, Sumer SO, Aksoy BA, Jacobsen A, Byrne CJ, Heuer ML, Larsson E, Antipin Y, Reva B, Goldberg AP, Sander C, Schultz N. 2012. The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discovery 2:401-404. doi: 10.1158/2159-8290. CD-12-0095.
10. Chi S, Kitanaka C, Noguchi K, Mochizuki T, Nagashima Y, Shirouzu M, Fujita H, Yoshida M, Chen W, Asai A, Himeno M, Yokoyama S, Kuchino Y. 1999. Oncogenic Ras triggers cell suicide through the activation of a caspaseindependent cell death program in human cancer cells. Oncogene 18:2281-2290. doi: 10.1038/sj.onc.1202538.
11. Chong CR, Janne PA. 2013. The quest to overcome resistance to EGFR-targeted therapies in cancer. Nature Medicine 19:1389-1400. doi: 10.1038/nm.3388.
12. Commisso C, Davidson SM, Soydaner-Azeloglu RG, Parker SJ, Kamphorst JJ, Hackett S, Grabocka E, Nofal M, Drebin JA, Thompson CB, Rabinowitz JD, Metallo CM, Vander Heiden MG, Bar-Sagi D. 2013. Macropinocytosis of protein is an amino acid supply route in Ras-transformed cells. Nature 497:633-637. doi: 10.1038/ nature12138.
13. Coso OA, Chiariello M, Yu JC, Teramoto H, Crespo P, Xu N, Miki T, Gutkind JS. 1995. The small GTP-binding proteins Rac1 and Cdc42 regulate the activity of the JNK/SAPK signaling pathway. Cell 81:1137-1146. doi: 10. 1016/S0092-8674(05)80018-2.
14. Ding L, Getz G, Wheeler DA, Mardis ER, McLellan MD, Cibulskis K, Sougnez C, Greulich H, Muzny DM, Morgan MB, Fulton L, Fulton RS, Zhang Q, Wendl MC, Lawrence MS, Larson DE, Chen K, Dooling DJ, Sabo A, Hawes AC, Shen H, Jhangiani SN, Lewis LR, Hall O, Zhu Y, Mathew T, Ren Y, Yao J, Scherer SE, Clerc K, Metcalf GA, Ng B, Milosavljevic A, Gonzalez-Garay ML, Osborne JR, Meyer R, Shi X, Tang Y, Koboldt DC, Lin L, Abbott R, Miner TL, Pohl C, Fewell G, Haipek C, Schmidt H, Dunford-Shore BH, Kraja A, Crosby SD, Sawyer CS, Vickery T, Sander S, Robinson J, Winckler W, Baldwin J, Chirieac LR, Dutt A, Fennell T, Hanna M, Johnson BE, Onofrio RC, Thomas RK, Tonon G, Weir BA, Zhao X, Ziaugra L, Zody MC, Giordano T, Orringer MB, Roth JA, Spitz MR, Wistuba II, Ozenberger B, Good PJ, Chang AC, Beer DG, Watson MA, Ladanyi M, Broderick S, Yoshizawa A, Travis WD, Pao W, Province MA, Weinstock GM, Varmus HE, Gabriel SB, Lander ES, Gibbs RA, Meyerson M, Wilson RK. 2008. Somatic mutations affect key pathways in lung adenocarcinoma. Nature 455:1069-1075. doi: 10.1038/ nature07423.
15. Efeyan A, Murga M, Martinez-Pastor B, Ortega-Molina A, Soria R, Collado M, Fernandez-Capetillo O, Serrano M. 2009. Limited role of murine ATM in oncogene-induced senescence and p53-dependent tumor suppression. PLOS ONE 4:e5475. doi: 10.1371/journal.pone.0005475.
16. Fisher GH, Wellen SL, Klimstra D, Lenczowski JM, Tichelaar JW, Lizak MJ, Whitsett JA, Koretsky A, Varmus HE. 2001. Induction and apoptotic regression of lung adenocarcinomas by regulation of a K-Ras transgene in the presence and absence of tumor suppressor genes. Genes & Development 15:3249-3262. doi: 10.1101/gad. 947701.
17. Gao J, Aksoy BA, Dogrusoz U, Dresdner G, Gross B, Sumer SO, Sun Y, Jacobsen A, Sinha R, Larsson E, Cerami E, Sander C, Schultz N. 2013. Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Science Signaling 6:pl1. doi: 10.1126/scisignal.2004088.
18. Gonda MA, Aaronson SA, Ellmore N, Zeve VH, Nagashima K. 1976. Ultrastructural studies of surface features of human normal and tumor cells in tissue culture by scanning and transmission electron microscopy. Journal of the National Cancer Institute 56:245-263.
19. Greulich H, Chen TH, Feng W, Janne PA, Alvarez JV, Zappaterra M, Bulmer SE, Frank DA, Hahn WC, Sellers WR, Meyerson M. 2005. Oncogenic transformation by inhibitor-sensitive and-resistant EGFR mutants. PLOS Medicine 2:e313. doi: 10.1371/journal.pmed.0020313.
20. Heist RS, Engelman JA. 2012. SnapShot: non-small cell lung cancer. Cancer Cell 21:448.e442. doi: 10.1016/j.ccr. 2012.03.007.
21. Hoadley KA, Yau C, Wolf DM, Cherniack AD, Tamborero D, Ng S, Leiserson MD, Niu B, McLellan MD, Uzunangelov V, Zhang J, Kandoth C, Akbani R, Shen H, Omberg L, Chu A, Margolin AA, Van't Veer LJ, Lopez-Bigas N, Laird PW, Raphael BJ, Ding L, Robertson AG, Byers LA, Mills GB, Weinstein JN, Van Waes C, Chen Z, Collisson EA, Cancer Genome Atlas Research Network, Benz CC, Perou CM, Stuart JM. 2014. Multiplatform analysis of 12 cancer types reveals molecular classification within and across tissues of origin. Cell 158:929-944. doi: 10.1016/j.cell.2014.06.049.
22. Imielinski M, Berger AH, Hammerman PS, Hernandez B, Pugh TJ, Hodis E, Cho J, Suh J, Capelletti M, Sivachenko A, Sougnez C, Auclair D, Lawrence MS, Stojanov P, Cibulskis K, Choi K, de Waal L, Sharifnia T, Brooks A, Greulich H, Banerji S, Zander T, Seidel D, Leenders F, Ansén S, Ludwig C, Engel-Riedel W, Stoelben E, Wolf J, Goparju C, Thompson K, Winckler W, Kwiatkowski D, Johnson BE, Jänne PA, Miller VA, Pao W, Travis WD, Pass HI, Gabriel SB, Lander ES, Thomas RK, Garraway LA, Getz G, Meyerson M. 2012. Mapping the hallmarks of lung adenocarcinoma with massively parallel sequencing. Cell 150:1107-1120. doi: 10.1016/j.cell.2012.08.029.
23. Irizarry RA, Hobbs B, Collin F, Beazer-Barclay YD, Antonellis KJ, Scherf U, Speed TP. 2003. Exploration, normalization, and summaries of high density oligonucleotide array probe level data. Biostatistics 4:249-264. doi: 10.1093/biostatistics/4.2.249.
24. Ji H, Ramsey MR, Hayes DN, Fan C, McNamara K, Kozlowski P, Torrice C, Wu MC, Shimamura T, Perera SA, Liang MC, Cai D, Naumov GN, Bao L, Contreras CM, Li D, Chen L, Krishnamurthy J, Koivunen J, Chirieac LR, Padera RF, Bronson RT, Lindeman NI, Christiani DC, Lin X, Shapiro GI, Jänne PA, Johnson BE, Meyerson M, Kwiatkowski DJ, Castrillon DH, Bardeesy N, Sharpless NE, Wong KK. 2007. LKB1 modulates lung cancer differentiation and metastasis. Nature 448:807-810. doi: 10.1038/nature06030.
25. Kandoth C, McLellan MD, Vandin F, Ye K, Niu B, Lu C, Xie M, Zhang Q, McMichael JF, Wyczalkowski MA, Leiserson MD, Miller CA, Welch JS, Walter MJ, Wendl MC, Ley TJ, Wilson RK, Raphael BJ, Ding L. 2013. Mutational landscape and significance across 12 major cancer types. Nature 502:333-339. doi: 10.1038/nature12634.
26. Khosravi-Far R, White MA, Westwick JK, Solski PA, Chrzanowska-Wodnicka M, Van Aelst L, Wigler MH, Der CJ. 1996. Oncogenic Ras activation of Raf/mitogen-activated protein kinase-independent pathways is sufficient to cause tumorigenic transformation. Molecular and Cellular Biology 16:3923-3933.
27. Kitambi SS, Toledo EM, Usoskin D, Wee S, Harisankar A, Svensson R, Sigmundsson K, Kalderén C, Niklasson M, Kundu S, Aranda S, Westermark B, Uhrbom L, Andäng M, Damberg P, Nelander S, Arenas E, Artursson P, Walfridsson J, Forsberg Nilsson K, Hammarström LG, Ernfors P. 2014. Vulnerability of glioblastoma cells to catastrophic vacuolization and death induced by a small molecule. Cell 157:313-328. doi: 10.1016/j.cell. 2014.02.021.
28. Lawrence MS, Stojanov P, Polak P, Kryukov GV, Cibulskis K, Sivachenko A, Carter SL, Stewart C, Mermel CH, Roberts SA, Kiezun A, Hammerman PS, McKenna A, Drier Y, Zou L, Ramos AH, Pugh TJ, Stransky N, Helman E, Kim J, Sougnez C, Ambrogio L, Nickerson E, Shefler E, Cortés ML, Auclair D, Saksena G, Voet D, Noble M, DiCara D, Lin P, Lichtenstein L, Heiman DI, Fennell T, Imielinski M, Hernandez B, Hodis E, Baca S, Dulak AM, Lohr J, Landau DA, Wu CJ, Melendez-Zajgla J, Hidalgo-Miranda A, Koren A, McCarroll SA, Mora J, Lee RS, Crompton B, Onofrio R, Parkin M, Winckler W, Ardlie K, Gabriel SB, Roberts CW, Biegel JA, Stegmaier K, Bass AJ, Garraway LA, Meyerson M, Golub TR, Gordenin DA, Sunyaev S, Lander ES, Getz G. 2013. Mutational heterogeneity in cancer and the search for new cancer-associated genes. Nature 499:214-218. doi: 10.1038/nature12213.
29. Lawrence MS, Stojanov P, Mermel CH, Robinson JT, Garraway LA, Golub TR, Meyerson M, Gabriel SB, Lander ES, Getz G. 2014. Discovery and saturation analysis of cancer genes across 21 tumour types. Nature 505:495-501. doi: 10.1038/nature12912.
30. Mahler JF, Stokes W, Mann PC, Takaoka M, Maronpot RR. 1996. Spontaneous lesions in aging FVB/N mice. Toxicologic Pathology 24:710-716. doi: 10.1177/019262339602400606.
31. Maltese WA, Overmeyer JH. 2014. Methuosis: nonapoptotic cell death associated with vacuolization of macropinosome and endosome compartments. The American Journal of Pathology 184:1630-1642. doi: 10. 1016/j.ajpath.2014.02.028.
32. Meerbrey KL, Hu G, Kessler JD, Roarty K, Li MZ, Fang JE, Herschkowitz JI, Burrows AE, Ciccia A, Sun T, Schmitt EM, Bernardi RJ, Fu X, Bland CS, Cooper TA, Schiff R, Rosen JM, Westbrook TF, Elledge SJ. 2011. The pINDUCER lentiviral toolkit for inducible RNA interference in vitro and in vivo. Proceedings of the National Academy of Sciences of USA 108:3665-3670. doi: 10.1073/pnas.1019736108.
33. Minden A, Lin A, Claret FX, Abo A, Karin M. 1995. Selective activation of the JNK signaling cascade and c-Jun transcriptional activity by the small GTPases Rac and Cdc42Hs. Cell 81:1147-1157. doi: 10.1016/S0092-8674(05) 80019-4.
34. Mizushima N. 2007. Autophagy: process and function. Genes & Development 21:2861-2873. doi: 10.1101/gad. 1599207.
35. Ohashi K, Sequist LV, Arcila ME, Moran T, Chmielecki J, Lin YL, Pan Y, Wang L, de Stanchina E, Shien K, Aoe K, Toyooka S, Kiura K, Fernandez-Cuesta L, Fidias P, Yang JC, Miller VA, Riely GJ, Kris MG, Engelman JA, Vnencak-Jones CL, Dias-Santagata D, Ladanyi M, Pao W. 2012. Lung cancers with acquired resistance to EGFR inhibitors occasionally harbor BRAF gene mutations but lack mutations in KRAS, NRAS, or MEK1. Proceedings of the National Academy of Sciences of USA 109:E2127-E2133. doi: 10.1073/pnas.1203530109.
36. Oliveros JC. 2007. VENNY. An interactive tool for comparing lists with Venn Diagrams.
37. Olson MF, Ashworth A, Hall A. 1995. An essential role for Rho, Rac, and Cdc42 GTPases in cell cycle progression through G1. Science 269:1270-1272. doi: 10.1126/science.7652575.
38. Overmeyer JH, Kaul A, Johnson EE, Maltese WA. 2008. Active ras triggers death in glioblastoma cells through hyperstimulation of macropinocytosis. Molecular Cancer Research 6:965-977. doi: 10.1158/1541-7786.MCR-07-2036.
39. Pao W, Miller V, Zakowski M, Doherty J, Politi K, Sarkaria I, Singh B, Heelan R, Rusch V, Fulton L, Mardis E, Kupfer D, Wilson R, Kris M, Varmus H. 2004. EGF receptor gene mutations are common in lung cancers from 'never smokers' and are associated with sensitivity of tumors to gefitinib and erlotinib. Proceedings of the National Academy of Sciences of USA 101:13306-13311. doi: 10.1073/pnas.0405220101.
40. Petti C, Molla A, Vegetti C, Ferrone S, Anichini A, Sensi M. 2006. Coexpression of NRASQ61R and BRAFV600E in human melanoma cells activates senescence and increases susceptibility to cell-mediated cytotoxicity. Cancer Research 66:6503-6511. doi: 10.1158/0008-5472.CAN-05-4671.
41. Podsypanina K, Politi K, Beverly LJ, Varmus HE. 2008. Oncogene cooperation in tumor maintenance and tumor recurrence in mouse mammary tumors induced by Myc and mutant Kras. Proceedings of the National Academy of Sciences of USA 105:5242-5247. doi: 10.1073/pnas.0801197105.
42. Politi K, Zakowski MF, Fan PD, Schonfeld EA, Pao W, Varmus HE. 2006. Lung adenocarcinomas induced in mice by mutant EGF receptors found in human lung cancers respond to a tyrosine kinase inhibitor or to down-regulation of the receptors. Genes & Development 20:1496-1510. doi: 10.1101/gad.1417406.
43. Sawyers CL. 2009. Finding and drugging the vulnerabilities of RAS-dependent cancers. Cell 137:796-798. doi: 10. 1016/j.cell.2009.05.011.
44. Sensi M, Nicolini G, Petti C, Bersani I, Lozupone F, Molla A, Vegetti C, Nonaka D, Mortarini R, Parmiani G, Fais S, Anichini A. 2006. Mutually exclusive NRASQ61R and BRAFV600E mutations at the single-cell level in the same human melanoma. Oncogene 25:3357-3364. doi: 10.1038/sj.onc.1209379.
45. Seo JS, Ju YS, Lee WC, Shin JY, Lee JK, Bleazard T, Lee J, Jung YJ, Kim JO, Shin JY, Yu SB, Kim J, Lee ER, Kang CH, Park IK, Rhee H, Lee SH, Kim JI, Kang JH, Kim YT. 2012. The transcriptional landscape and mutational profile of lung adenocarcinoma. Genome Research 22:2109-2119. doi: 10.1101/gr.145144.112.
46. Sharifnia T, Rusu V, Piccioni F, Bagul M, Imielinski M, Cherniack AD, Pedamallu CS, Wong B, Wilson FH, Garraway LA, Altshuler D, Golub TR, Root DE, Subramanian A, Meyerson M. 2014. Genetic modifiers of EGFR dependence in non-small cell lung cancer. Proceedings of the National Academy of Sciences of USA 111:18661-18666. doi: 10.1073/pnas.1412228112.
47. Song X, Fan PD, Bantikassegn A, Guha U, Threadgill DW, Varmus H, Politi K. 2015. ERBB3 independent activation of the PI3K pathway in EGFR mutant lung adenocarcinomas. Cancer Research 75:1035-1045. doi: 10.1158/0008-5472.CAN-13-1625.
48. Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, Paulovich A, Pomeroy SL, Golub TR, Lander ES, Mesirov JP. 2005. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proceedings of the National Academy of Sciences of USA 102:15545-15550. doi: 10.1073/pnas.0506580102.
49. Sunaga N, Shames DS, Girard L, Peyton M, Larsen JE, Imai H, Soh J, Sato M, Yanagitani N, Kaira K, Xie Y, Gazdar AF, Mori M, Minna JD. 2011. Knockdown of oncogenic KRAS in non-small cell lung cancers suppresses tumor growth and sensitizes tumor cells to targeted therapy. Molecular Cancer Therapeutics 10:336-346. doi: 10.1158/ 1535-7163.MCT-10-0750.
50. Taketo M, Schroeder AC, Mobraaten LE, Gunning KB, Hanten G, Fox RR, Roderick TH, Stewart CL, Lilly F, Hansen CT. 1991. FVB/N: an inbred mouse strain preferable for transgenic analyses. Proceedings of the National Academy of Sciences of USA 88:2065-2069. doi: 10.1073/pnas.88.6.2065.
51. Wong TN, Ramsingh G, Young AL, Miller CA, Touma W, Welch JS, Lamprecht TL, Shen D, Hundal J, Fulton RS, Heath S, Baty JD, Klco JM, Ding L, Mardis ER, Westervelt P, DiPersio JF, Walter MJ, Graubert TA, Ley TJ, Druley TE, Link DC, Wilson RK. 2014. Role of TP53 mutations in the origin and evolution of therapy-related acute myeloid leukaemia. Nature 518:552-555. doi: 10.1038/nature13968.
52. Yu HA, Arcila ME, Rekhtman N, Sima CS, Zakowski MF, Pao W, Kris MG, Miller VA, Ladanyi M, Riely GJ. 2013. Analysis of tumor specimens at the time of acquired resistance to EGFR-TKI therapy in 155 patients with EGFRmutant lung cancers. Clinical Cancer Research 19:2240-2247. doi: 10.1158/1078-0432.CCR-12-2246.