REFERENCES
1. Hsieh JJ, Purdue MP, Signoretti S, Swanton C, Albiges L, et al. Renal cell carcinoma. Nat Rev Dis Primers 2017;3:17009.
3. Hakimi AA, Reznik E, Lee CH, Creighton CJ, Brannon AR, et al. An integrated metabolic atlas of clear cell renal cell carcinoma. Cancer Cell 2016;29:104-16.
4. Cancer Genome Atlas Research Network. Comprehensive molecular characterization of clear cell renal cell carcinoma. Nature 2013;499:43-9.
5. Hsieh JJ, Le V, Cao D, Cheng E. Genomic classifications of renal cell carcinoma: a critical step towards the future personalized kidney cancer care with pan-omics precision. J Pathol 2018;244:525-37.
6. Hsieh JJ, Manley BJ, Khan N, Gao J, Carlo MI, et al. Overcome tumor heterogeneity-imposed therapeutic barriers through convergent genomic biomarker discovery: a braided cancer river model of kidney cancer. Semin Cell Dev Biol 2017;64:98-106.
7. Semenza GL. HIF-1 mediates metabolic responses to intratumoral hypoxia and oncogenic mutations. J Clin Invest 2013;123:3664-71.
8. Masson N, Ratcliffe PJ. Hypoxia signaling pathways in cancer metabolism: the importance of co-selecting interconnected physiological pathways. Cancer Metab 2014;2:3.
9. Courtney KD, Infante JR, Lam ET, Choueiri TK. Phase I dose-escalation trial of PT2385, a first-in-class hypoxia-inducible factor-2α antagonist in patients with previously treated advanced clear cell renal cell carcinoma. J Clin Onc 2018;36:867-74.
10. Hakimi AA, Tickoo SK, Jacobsen A, Sarungbam J, Sfakianos JP, et al. TCEB1-mutated renal cell carcinoma: a distinct genomic and morphological subtype. Mod Pathol 2015;28:845-53.
11. Kibel A, Iliopoulous O, DeCaprio JA, Kaelin WG Jr. Binding of the von Hippel-Lindau tumor suppressor protein to Elong B and C. Science 1995;269:1444-6.
12. Rohan SM, Xiao Y, Liang Y, Dudas ME, Al-Ahmadie HA, et al. Clear-cell papillary renal cell carcinoma: molecular and immunohistochemical analysis with emphasis on the von Hippel-Lindau gene and hypoxia-inducible factor pathway related proteins. Mod Pathol 2011;24:1207-20.
13. Carroll VA, Ashcroft M. Role of hypoxia-induced factor (HIF)-1 alpha versus HIF-2 alpha in regulation of HIF target genes in response to hypoxia, insulin-like growth factor-I, or loss of von Hippel-Lindau function: implications for targeting the pathway. Cancer Res 2006;66:6264-70.
14. Shen C, Kaelin WG. The VHL/HIF axis in clear cell renal carcinoma. Semin Cancer Biol 2013;23:18-25.
15. Semenza GL. Defining the role of hypoxia-inducible factor 1 in cancer biology and therapeutics. Oncogene 2010;29:625-34.
16. Fu L, Wang G, Shevchuk MM, Nanus DM, Gudas LJ. Generation of a mouse model of Von Hippel-Lindau kidney disease leading to renal cancers by expression of a constitutively active mutant of HIF1alpha. Cancer Res 2011;71:6848-56.
17. Fu L, Wang G, Shevchuk MM, Nanus DM, Gudas LJ. Activation of HIF2alpha in kidney proximal tubule cells causes abnormal glyogen deposition but not tumorgenesis. Cancer Res 2013;73:2916-25.
18. Kondo K, Clco J, Nakamura E, Kaelin WG. Inhibition of HIF is necessary for tumor suppression by von Hippel-Lindau protein. Cancer Cell 2002;1:237-46.
19. Zimmer M, Doucette D, Siddiqui N, Iliopoulous O. Inhibition of hypoxia-inducible factor is sufficient for growth suppression of VHL -/- tumors. Mol Cancer Res 2004;2:89-95.
20. Purdue MP, Johansson M, Zelenika D, Toro JR. Genome-wide association study of renal cell carcinoma identifies two susceptibility loci on 2p21 and 11q13.3. Nat Genet 2011;43:60-5.
21. Kroeger N, Klatte T, Chamie K, Rao PN. Deletions of chromosomes 3p and 14q molecularly subclassify clear cell renal cell carcinoma. Cancer 2013;119:1547-54.
22. Motzer RJ, Jonasch E, Agarwal N, Bhayani S, Bro WP, et al. Kidney Cancer, Version 2.2017, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 2017;15:804-34.
23. Rodgers JL, Bayeh L, Scheuermann TH, Longgood J, Key J, et al. Development of inhibitors of the PAS-B domain of the HIF-2α transcription factor. J Med Chem 2013;56:1739-47.
24. Wallace EM, Rizzi JP, Han G, Wehn PM, Cao Z, et al. A small molecule antagonist of HIF-2α is efficacious in pre-clinical models of renal cell carcinoma. Cancer Res 2016;76:5491-500.
25. Kapitsinou PP, Haase VH. The VHL tumor suppressor and HIF: insights from genetic studies in mice. Cell Death Differ 2008;15:650-9.
26. Cancer Genome Atlas Research Network. Comprehensive molecular profiling of lung adenocarcinoma. Nature 2014;511:543-50.
27. Hakimi AA, Chen YB, Wren J, Gonen M, Abdel-Wahab O, et al. Clinical and pathologic impact of select chromatin-modulating tumor suppressors in clear cell renal cell carcinom. Eur Urol 2013;63:848-54.
28. Pena-Llopis S, Vega-Rubin-de-Celis S, Liao A, Leng N, Pavía-Jiménez A, et al. BAP1 loss defines a new class of renal cell carcinoma. Nat Genet 2012;44:751-9.
29. Varela I, Tarpey P, Raine K, Huang D, Ong CK, et al. Exome sequencing identifies frequent mutation of SWI/SNF complex gene PBRM1 in renal carcinoma. Nature 2011;469:539-42.
30. Nargund AM, Pham CG, Dong Y, Wang PI, Osmangeyoglu HU, et al. The SWI/SNF protein PBRM1 restrains VHL-loss-driven clear cell renal cell carcinoma. Cell Rep 2017;18:2893-906.
31. Biegel JA, Busse TM, Weissman BE. SWI/SNF chromatin remodeling complexes and cancer. Am J Med Genet 2014;166:350-66.
32. Hargreaves DC, Crabtree GR. ATP-dependent chromatin remodeling genetics, genomics, and mechanisms. Cell Res 2011;21:396-420.
33. Kadoch C, Hargreaves DC, Hodges C, Elias L, Ho L, et al. Proteomic and bioinformatic analysis of mammalian SWI/SNF complexes identifies extensive roles in human malignancy. Nat Genet 2013;45:592-601.
35. Gao W, Li W, Xiao T, Liu XS, Kaelin WG Jr. Inactivation of the PBRM1 tumor suppressor gene amplifies the HIF-response in VHL -/- clear cell renal carcinoma. Proc Natl Acad Sci USA 2017;114:1027-32.
36. Saxton RA, Sabatini DM. mTOR signaling in growth, metabolism, and disease. Cell 2017;169:361-71.
37. Brugarolas J, Lei K, Hurley RL, Manning BD, Reiling JH, et al. Regulation of mTOR function in response to hypoxia by REDD1 and the TSC1/SC2 tumor suppressor complex. Genes Dev 2004;18:2893-904.
38. Robb V, Karbowniczek M, Szanto AJ, Henske EP. Activation of the mTOR signaling pathway in renal clear cell carcinoma. J Urol 2007;177:346-52.
39. Wei EY, Hsieh JJ. A river model to map convergent cancer evolution and guide therapy in RCC. Nat Rev Urol 2015;12:706-12.
40. Hsieh JJ, Chen D, Wang PI, Marker M, Redzematovic A, et al. Genomic biomarkers of a randomized trial comparing first-line everolimus and sunitinib in patients with metastatic renal cell carcinoma. Eur Urol 2017;71:405-14.
41. Hsieh JJ, Chen DPW, Chen YB, Redzematovic A, Marker M. Identification of efficacy biomarkers in a large metastatic renal cell carcinoma (mRCC) cohort through next generation sequencing (NGS): results from RECORD-3. J Clin Oncol 2015;33:abstr4509.
42. Voss MH, Hsieh JJ. Therapeutic guide for mTOuRing through the braided kidney cancer genomic river. Clin Cancer Res 2016;22:2320-2.
43. Kwiatkowski DJ, Choueiri TK, Fay AP, Rini BI, Thorner AR, et al. Muttions in TSC1, TSC2, and MTOR are associated with response to rapalogs in patients with metastatic renal cell carcinoma. Clin Cancer Res 2016;22:2445-52.
44. Nargund AM, Ozmanbeyoglu HU, Cheng EH, Hsieh JJ. SWI/SNF tumor suppressor gene PBRM1/BAF180 in human clear cell kidney cancer. Mol Cell Oncol 2017;4:e1342747.
45. Dalgliesh GL, Furge K, Greenman C, Chen L, Bignell G, et al. Systematic sequencing of renal carcinoma reveals inactivation of histone modifying enzymes. Nature 2010;463:360-3.
46. Sun XJ, Wu J, Wei XY, Hu M, Wang L. Identification and characterization of a novel human histone H3 lysine 36-specific methyltransferase. J Biol Chem 2005;280:35261-71.
47. Simon JM, Hacker KE, Singh D, Brannon AR, Parker JS. Variation in chromatin accessibility in human kidney cancer links H3K36 methyltransferase loss with widespread RNA processing defects. Genome Res 2014;24:241-50.
48. Sarakbi AW, Sasi W, Jiang WG, Roberts T, Newbold RF, et al. The mRNA expression of SETD2 in human breast cancer: correlation with clinico-pathological parameters. BMC Cancer 2009;9:290.
49. Zhang J, ding L, Holmfeldt L, Wu G, Heatley SL, et al. The genetic basis of early T-cell precursor acute lymphoblastic leukemia. Nature 2012;481:157-63.
50. Xiang W, He J, Huang C, Chen L, Tao D, et al. miR-106b-5p targets tumor suppressor gene SETD2 to inactive its function in clear cell renal cell carcinoma. Oncotarget 2015;6:4066-79.
51. Duns G, van-der-Berg E, van-Duivenbode I, Osinga J, Hollema H, et al. Histone methyltransferase gene SETD2 is a novel tumor suppressor gene in clear cell renal carcinoma. Cancer Res 2010;70:4287-91.
52. Manley BJ, Zabor EC, Casuscelli J, Tennenbaum DM, Redzematovic A, et al. Integration of recurrent somatic mutations with clinical outcomes: a pooled analysis of 1049 patients with clear cell renal cell carcinoma. Eur Urol Focus 2017;3:421-7.
53. Tennenbaum DM, Manley BJ, Zabor E, Becerra MF, Carlo MI, et al. Genomic alterations as predictors of survival among patients within a combined cohort with clear cell renal cell carcinoma undergoing cytoreductive nephrectomy. Urol Oncol 2017;35:532.
54. Gerlinger M, Rowan AJ, Horswell S, Math M, Larkin J, et al. Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med 2012;366:883-92.
55. Nishikawa H, Wu W, Koike A, Kojima R, Gomi H, et al. BRCA1-associated protein 1 interferes with BRCA1/BARD1 RING heterodimer activity. Cancer Res 2009;69:111-9.
56. Mallery DL, Vandenberg CJ, Hiom K. Activation of the E3 ligase function of the BRCA1/BARD1 complex by polyubiquitin chains. EMBO J 2002;21:6755-62.
57. Piva F, Santoni M, Matrana MR, Satti S, Giulietti M, et al. BAP1, PBRM1 and SETD2 in clear-cell renal cell carcinoma: molecular diagnostics and possible targets for personalized therapies. Expert Rev Mol Diagn 2015;15:1201-10.
58. Wang SS, Gu YF, Wolff N, Stefanius K, Christie A, et al. Bap1 is essential for kidney function and cooperates with VHL in renal tumorigenesis. Proc Natl Acad Sci USA 2014;111:16538-43.
59. Choueiri TK, Escudier B, Powles T, Tannir NM, Mainwaring PN, et al. Cabozantinib versus everolimus in advanced renal-cell carcinoma. N Engl J Med 2015;373:1814-23.
60. Escudier B, Eisen T, Stadler WM, Szczylik C, Oudard S, et al. Sorafenib in advanced clear cell renal cell carcinoma. N Engl J Med 2007;357:203.
61. Motzer RJ, Hutson TE, Glen H, Michaelson MD, Molina A, et al. Lenvatinib, everolimus, and the combination in patients with metastatic renal cell carcinoma: a randomised, phase 2, open-label, multicentre trial. Lancet Oncol 2015;16:1473-82.
62. Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, et al. Sunitinb versus interferon alfa in metastatic renal cell carcinoma. N Engl J Med 2007;356:115-24.
63. Motzer RJ, McCann L, Deen K. Pazopanib versus sunitinib in renal cancer. N Engl J Med 2013;369:1970.
64. Rini BI, Escudier B, Tomczak P, Kaprin A, Szczylik C, et al. Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial. Lancet 2011;378:1931-9.
65. Escudier B, PLuzanska A, Koralewski P, Ravaud A, Bracarda S, et al. Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial. Lancet 2007;370:2103-11.
66. Hudes G, Carducci M, Tomczak P. Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med 2007;356:2271-81.
67. Motzer RJ, Escudier B, Oudard S, Hutson TE, Porta C, et al. Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet 2008;372:449-56.
68. McDermott DF, Regan MM, Clark JI, Flaherty LE, Weiss GR, et al. Randomized phase III trial of high-dose interleukin-2 versus subcutaneous interleukin-2 and interferon in patients with metastatic renal cell carcinoma. J Clin Oncol 2005;23:133-41.
69. Motzer RJ, Escudier B, McDermott DF, George S, Hammers HJ, et al. Nivolumab versus everolimus in advanced renal-cell carcinoma. N Engl J Med 2015;373:1803-13.