Cancer gene profiling in non-small cell lung cancers reveals activating mutations in JAK2 and JAK3 with therapeutic implications

Genome Medicine

Volumn 9, Issue 1, 2017, Pages

  Li, Shuyu D ^a,b   Ma, Meng ^a,b   Li, Hui ^a,b   Waluszko, Aneta ^a   Sidorenko, Tatyana ^a   Schadt, Eric E ^a,b   Zhang, David Y ^a   Chen, Rong ^a,b   Ye, Fei ^a,c  

^a MOUNT SINAI SCHOOL OF MEDICINE   (United States)

^b a Mount Sinai venture ^*  (United States)

^c NEW YORK MEDICAL COLLEGE   (United States)

Author keywords

Cancer hotspot panel; Clinical sequencing; Immunotherapy; JAK2; JAK3; Non small cell lung cancer

Indexed keywords

JANUS KINASE 2; JANUS KINASE 3; PROGRAMMED DEATH 1 LIGAND 1; ANTINEOPLASTIC AGENT; ENZYME INHIBITOR; JAK2 PROTEIN, HUMAN; JAK3 PROTEIN, HUMAN; PDCD1 PROTEIN, HUMAN; PROGRAMMED DEATH 1 RECEPTOR; TRANSCRIPTOME;

ARTICLE; CONTROLLED STUDY; DISEASE ASSOCIATION; GENE EXPRESSION PROFILING; GENE FREQUENCY; GERMLINE MUTATION; HUMAN; HUMAN TISSUE; JAK2 GENE; JAK3 GENE; MAJOR CLINICAL STUDY; MUTATIONAL ANALYSIS; MYELOPROLIFERATIVE NEOPLASM; NEXT GENERATION SEQUENCING; NON SMALL CELL LUNG CANCER; PRIORITY JOURNAL; PROTEIN EXPRESSION; SOMATIC MUTATION; UPREGULATION; ANTAGONISTS AND INHIBITORS; ENZYMOLOGY; GENETICS; HIGH THROUGHPUT SEQUENCING; IMMUNOLOGY; IMMUNOTHERAPY; LUNG TUMOR; MUTATION;

ANTINEOPLASTIC AGENTS; CARCINOMA, NON-SMALL-CELL LUNG; ENZYME INHIBITORS; GERM-LINE MUTATION; HIGH-THROUGHPUT NUCLEOTIDE SEQUENCING; HUMANS; IMMUNOTHERAPY; JANUS KINASE 2; JANUS KINASE 3; LUNG NEOPLASMS; MUTATION; PROGRAMMED CELL DEATH 1 RECEPTOR; TRANSCRIPTOME;

EID: 85032572489     PISSN: None     EISSN: 1756994X     Source Type: Journal    
DOI: 10.1186/s13073-017-0478-1     Document Type: Article

References (60)

1. Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2017. CA Cancer J Clin. 2017;67(1):7-30. doi: 10.3322/caac.21387.
2. Travis WD, Brambilla E, Nicholson AG, Yatabe Y, Austin JH, Beasley MB, et al. The 2015 World Health Organization Classification of Lung Tumors: Impact of Genetic, Clinical and Radiologic Advances Since the 2004 Classification. J Thorac Oncol. 2015;10(9):1243-60. doi: 10.1097/jto.0000000000000630.
3. Cancer Genome Atlas Research Network. Comprehensive genomic characterization of squamous cell lung cancers. Nature. 2012;489(7417):519-25. doi: 10.1038/nature11404.
4. Cancer Genome Atlas Research Network. Comprehensive molecular profiling of lung adenocarcinoma. Nature. 2014;511(7511):543-50. doi: 10.1038/nature13385.
5. Campbell JD, Alexandrov A, Kim J, Wala J, Berger AH, Pedamallu CS, et al. Distinct patterns of somatic genome alterations in lung adenocarcinomas and squamous cell carcinomas. Nat Genet. 2016;48(6):607-16. doi: 10.1038/ng.3564.
6. George J, Lim JS, Jang SJ, Cun Y, Ozretic L, Kong G, et al. Comprehensive genomic profiles of small cell lung cancer. Nature. 2015;524(7563):47-53. doi: 10.1038/nature14664.
7. Govindan R, Ding L, Griffith M, Subramanian J, Dees ND, Kanchi KL, et al. Genomic landscape of non-small cell lung cancer in smokers and never-smokers. Cell. 2012;150(6):1121-34. doi: 10.1016/j.cell.2012.08.024.
8. Gautschi O, Milia J, Cabarrou B, Bluthgen MV, Besse B, Smit EF, et al. Targeted therapy for patients with BRAF-mutant lung cancer: results from the European EURAF Cohort. J Thorac Oncol. 2015;10(10):1451-7. doi: 10.1097/jto.0000000000000625.
9. Hyman DM, Puzanov I, Subbiah V, Faris JE, Chau I, Blay JY, et al. Vemurafenib in multiple nonmelanoma cancers with BRAF V600 mutations. N Engl J Med. 2015;373(8):726-36. doi: 10.1056/NEJMoa1502309.
10. Planchard D, Besse B, Groen HJ, Souquet PJ, Quoix E, Baik CS, et al. Dabrafenib plus trametinib in patients with previously treated BRAF(V600E)-mutant metastatic non-small cell lung cancer: an open-label, multicentre phase 2 trial. Lancet Oncol. 2016;17(7):984-93. doi: 10.1016/s1470-2045(16)30146-2.
11. Planchard D, Kim TM, Mazieres J, Quoix E, Riely G, Barlesi F, et al. Dabrafenib in patients with BRAF(V600E)-positive advanced non-small-cell lung cancer: a single-arm, multicentre, open-label, phase 2 trial. Lancet Oncol. 2016;17(5):642-50. doi: 10.1016/s1470-2045(16)00077-2.
12. Awad MM, Oxnard GR, Jackman DM, Savukoski DO, Hall D, Shivdasani P, et al. MET Exon 14 mutations in non-small-cell lung cancer are associated with advanced age and stage-dependent MET genomic amplification and c-Met overexpression. J Clin Oncol. 2016;34(7):721-30. doi: 10.1200/jco.2015.63.4600.
13. Frampton GM, Ali SM, Rosenzweig M, Chmielecki J, Lu X, Bauer TM, et al. Activation of MET via diverse exon 14 splicing alterations occurs in multiple tumor types and confers clinical sensitivity to MET inhibitors. Cancer Dis. 2015;5(8):850-9. doi: 10.1158/2159-8290.cd-15-0285.
14. Paik PK, Drilon A, Fan PD, Yu H, Rekhtman N, Ginsberg MS, et al. Response to MET inhibitors in patients with stage IV lung adenocarcinomas harboring MET mutations causing exon 14 skipping. Cancer Dis. 2015;5(8):842-9. doi: 10.1158/2159-8290.cd-14-1467.
15. Drilon A, Rekhtman N, Arcila M, Wang L, Ni A, Albano M, et al. Cabozantinib in patients with advanced RET-rearranged non-small-cell lung cancer: an open-label, single-centre, phase 2, single-arm trial. Lancet Oncol. 2016;17(12):1653-60. doi: 10.1016/s1470-2045(16)30562-9.
16. Drilon A, Wang L, Hasanovic A, Suehara Y, Lipson D, Stephens P, et al. Response to Cabozantinib in patients with RET fusion-positive lung adenocarcinomas. Cancer Dis. 2013;3(6):630-5. doi: 10.1158/2159-8290.cd-13-0035.
17. Cappuzzo F, Bemis L, Varella-Garcia M. HER2 mutation and response to trastuzumab therapy in non-small-cell lung cancer. N Engl J Med. 2006;354(24):2619-21. doi: 10.1056/NEJMc060020.
18. Mazieres J, Peters S, Lepage B, Cortot AB, Barlesi F, Beau-Faller M, et al. Lung cancer that harbors an HER2 mutation: epidemiologic characteristics and therapeutic perspectives. J Clin Oncol. 2013;31(16):1997-2003. doi: 10.1200/jco.2012.45.6095.
19. Suh JH, Johnson A, Albacker L, Wang K, Chmielecki J, Frampton G, et al. Comprehensive genomic profiling facilitates implementation of the National Comprehensive Cancer Network guidelines for lung cancer biomarker testing and identifies patients who may benefit from enrollment in mechanism-driven clinical trials. Oncologist. 2016;21(6):684-91. doi: 10.1634/theoncologist.2016-0030.
20. NCI Prepares to Launch MATCH Trial. Cancer Dis. 2015;5(7):685. doi: 10.1158/2159-8290.cd-nb2015-052.
21. Cerami E, Gao J, Dogrusoz U, Gross BE, Sumer SO, Aksoy BA, et al. The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Dis. 2012;2(5):401-4. doi: 10.1158/2159-8290.cd-12-0095.
22. Gao J, Aksoy BA, Dogrusoz U, Dresdner G, Gross B, Sumer SO, et al. Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci Signal. 2013;6(269):11. doi: 10.1126/scisignal.2004088.
23. Mok TS, Wu YL, Ahn MJ, Garassino MC, Kim HR, Ramalingam SS, et al. Osimertinib or platinum-pemetrexed in EGFR T790M-positive lung cancer. N Engl J Med. 2017;376(7):629-40. doi: 10.1056/NEJMoa1612674.
24. Sen B, Peng S, Tang X, Erickson HS, Galindo H, Mazumdar T, et al. Kinase-impaired BRAF mutations in lung cancer confer sensitivity to dasatinib. Sci Transl Med. 2012;4(136):136ra70. doi: 10.1126/scitranslmed.3003513.
25. Baxter EJ, Scott LM, Campbell PJ, East C, Fourouclas N, Swanton S, et al. Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet. 2005;365(9464):1054-61. doi: 10.1016/s0140-6736(05)71142-9.
26. Kralovics R, Passamonti F, Buser AS, Teo SS, Tiedt R, Passweg JR, et al. A gain-of-function mutation of JAK2 in myeloproliferative disorders. N Engl J Med. 2005;352(17):1779-90. doi: 10.1056/NEJMoa051113.
27. Levine RL, Wadleigh M, Cools J, Ebert BL, Wernig G, Huntly BJ, et al. Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis. Cancer Cell. 2005;7(4):387-97. doi: 10.1016/j.ccr.2005.03.023.
28. Chen E, Staudt LM, Green AR. Janus kinase deregulation in leukemia and lymphoma. Immunity. 2012;36(4):529-41. doi: 10.1016/j.immuni.2012.03.017.
29. Vainchenker W, Constantinescu SN. JAK/STAT signaling in hematological malignancies. Oncogene. 2013;32(21):2601-13. doi: 10.1038/onc.2012.347.
30. Thomas SJ, Snowden JA, Zeidler MP, Danson SJ. The role of JAK/STAT signalling in the pathogenesis, prognosis and treatment of solid tumours. Br J Cancer. 2015;113(3):365-71. doi: 10.1038/bjc.2015.233.
31. Quintas-Cardama A, Verstovsek S. Molecular pathways: Jak/STAT pathway: mutations, inhibitors, and resistance. Clin Cancer Res. 2013;19(8):1933-40. doi: 10.1158/1078-0432.ccr-12-0284.
32. Garnett MJ, Edelman EJ, Heidorn SJ, Greenman CD, Dastur A, Lau KW, et al. Systematic identification of genomic markers of drug sensitivity in cancer cells. Nature. 2012;483(7391):570-5. doi: 10.1038/nature11005.
33. Yang W, Soares J, Greninger P, Edelman EJ, Lightfoot H, Forbes S, et al. Genomics of Drug Sensitivity in Cancer (GDSC): a resource for therapeutic biomarker discovery in cancer cells. Nucleic Acids Res. 2013;41(Database issue):D955-61. doi: 10.1093/nar/gks1111.
34. Pardanani A, Harrison C, Cortes JE, Cervantes F, Mesa RA, Milligan D, et al. Safety and efficacy of fedratinib in patients with primary or secondary myelofibrosis: a randomized clinical trial. JAMA Oncol. 2015;1(5):643-51. doi: 10.1001/jamaoncol.2015.1590.
35. Shin DS, Zaretsky JM, Escuin-Ordinas H, Garcia-Diaz A, Hu-Lieskovan S, Kalbasi A, et al. Primary resistance to PD-1 blockade mediated by JAK1/2 mutations. Cancer Dis. 2017;7(2):188-201. doi: 10.1158/2159-8290.cd-16-1223.
36. Zaretsky JM, Garcia-Diaz A, Shin DS, Escuin-Ordinas H, Hugo W, Hu-Lieskovan S, et al. Mutations associated with acquired resistance to PD-1 blockade in melanoma. N Engl J Med. 2016;375(9):819-29. doi: 10.1056/NEJMoa1604958.
37. Masago K, Fujita S, Muraki M, Hata A, Okuda C, Otsuka K, et al. Next-generation sequencing of tyrosine kinase inhibitor-resistant non-small-cell lung cancers in patients harboring epidermal growth factor-activating mutations. BMC Cancer. 2015;15:908. doi: 10.1186/s12885-015-1925-2.
38. Silva IP, Salhi A, Giles KM, Vogelsang M, Han SW, Ismaili N, et al. Identification of a novel pathogenic germline KDR variant in melanoma. Clin Cancer Res. 2016;22(10):2377-85. doi: 10.1158/1078-0432.ccr-15-1811.
39. Walters DK, Mercher T, Gu TL, O'Hare T, Tyner JW, Loriaux M, et al. Activating alleles of JAK3 in acute megakaryoblastic leukemia. Cancer Cell. 2006;10(1):65-75. doi: 10.1016/j.ccr.2006.06.002.
40. Van Allen EM, Golay HG, Liu Y, Koyama S, Wong K, Taylor-Weiner A, et al. Long-term benefit of PD-L1 blockade in lung cancer associated with JAK3 activation. Cancer Immunol Res. 2015;3(8):855-63. doi: 10.1158/2326-6066.cir-15-0024.
41. Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, et al. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med. 2015;372(26):2509-20. doi: 10.1056/NEJMoa1500596.
42. Rizvi NA, Hellmann MD, Snyder A, Kvistborg P, Makarov V, Havel JJ, et al. Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science (New York, NY). 2015;348(6230):124-8. doi: 10.1126/science.aaa1348.
43. Martinaud C, Brisou P, Mozziconacci MJ. Is the JAK2(V617F) mutation detectable in healthy volunteers? Am J Hematol. 2010;85(4):287-8. doi: 10.1002/ajh.21627.
44. Sidon P, El Housni H, Dessars B, Heimann P. The JAK2V617F mutation is detectable at very low level in peripheral blood of healthy donors. Leukemia. 2006;20(9):1622. doi: 10.1038/sj.leu.2404292.
45. Lipson D, Capelletti M, Yelensky R, Otto G, Parker A, Jarosz M, et al. Identification of new ALK and RET gene fusions from colorectal and lung cancer biopsies. Nat Med. 2012;18(3):382-4. doi: 10.1038/nm.2673.
46. Imielinski M, Greulich H, Kaplan B, Araujo L, Amann J, Horn L, et al. Oncogenic and sorafenib-sensitive ARAF mutations in lung adenocarcinoma. J Clin Invest. 2014;124(4):1582-6. doi: 10.1172/jci72763.
47. Kim Y, Hammerman PS, Kim J, Yoon JA, Lee Y, Sun JM, et al. Integrative and comparative genomic analysis of lung squamous cell carcinomas in East Asian patients. J Clin Oncol. 2014;32(2):121-8. doi: 10.1200/jco.2013.50.8556.
48. Li S, Choi YL, Gong Z, Liu X, Lira M, Kan Z, et al. Comprehensive characterization of oncogenic drivers in Asian lung adenocarcinoma. J Thorac Oncol. 2016;11(12):2129-40. doi: 10.1016/j.jtho.2016.08.142.
49. Seo JS, Ju YS, Lee WC, Shin JY, Lee JK, Bleazard T, et al. The transcriptional landscape and mutational profile of lung adenocarcinoma. Genome Res. 2012;22(11):2109-19. doi: 10.1101/gr.145144.112.
50. Wu K, Zhang X, Li F, Xiao D, Hou Y, Zhu S, et al. Frequent alterations in cytoskeleton remodelling genes in primary and metastatic lung adenocarcinomas. Nat Commun. 2015;6:10131. doi: 10.1038/ncomms10131.
51. Steensma DP, Bejar R, Jaiswal S, Lindsley RC, Sekeres MA, Hasserjian RP, et al. Clonal hematopoiesis of indeterminate potential and its distinction from myelodysplastic syndromes. Blood. 2015;126(1):9-16. doi: 10.1182/blood-2015-03-631747.
52. Genovese G, Kahler AK, Handsaker RE, Lindberg J, Rose SA, Bakhoum SF, et al. Clonal hematopoiesis and blood-cancer risk inferred from blood DNA sequence. N Engl J Med. 2014;371(26):2477-87. doi: 10.1056/NEJMoa1409405.
53. Jaiswal S, Fontanillas P, Flannick J, Manning A, Grauman PV, Mar BG, et al. Age-related clonal hematopoiesis associated with adverse outcomes. N Engl J Med. 2014;371(26):2488-98. doi: 10.1056/NEJMoa1408617.
54. Jaiswal S, Natarajan P, Silver AJ, Gibson CJ, Bick AG, Shvartz E, et al. Clonal hematopoiesis and risk of atherosclerotic cardiovascular disease. N Engl J Med. 2017;377(2):111-21. doi: 10.1056/NEJMoa1701719.
55. Xie M, Lu C, Wang J, McLellan MD, Johnson KJ, Wendl MC, et al. Age-related mutations associated with clonal hematopoietic expansion and malignancies. Nat Med. 2014;20(12):1472-8. doi: 10.1038/nm.3733.
56. Gao SP, Chang Q, Mao N, Daly LA, Vogel R, Chan T, et al. JAK2 inhibition sensitizes resistant EGFR-mutant lung adenocarcinoma to tyrosine kinase inhibitors. Sci Signal. 2016;9(421):ra33. doi: 10.1126/scisignal.aac8460.
57. Gao SP, Mark KG, Leslie K, Pao W, Motoi N, Gerald WL, et al. Mutations in the EGFR kinase domain mediate STAT3 activation via IL-6 production in human lung adenocarcinomas. J Clin Invest. 2007;117(12):3846-56. doi: 10.1172/jci31871.
58. Chuang CH, Greenside PG, Rogers ZN, Brady JJ, Yang D, Ma RK, et al. Molecular definition of a metastatic lung cancer state reveals a targetable CD109-Janus kinase-Stat axis. Nat Med. 2017;23(3):291-300. doi: 10.1038/nm.4285.
59. Borghaei H, Paz-Ares L, Horn L, Spigel DR, Steins M, Ready NE, et al. Nivolumab versus Docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med. 2015;373(17):1627-39. doi: 10.1056/NEJMoa1507643.
60. Motzer RJ, Escudier B, McDermott DF, George S, Hammers HJ, Srinivas S, et al. Nivolumab versus Everolimus in advanced renal-cell carcinoma. N Engl J Med. 2015;373(19):1803-13. doi: 10.1056/NEJMoa1510665.