Implementing precision cancer medicine in the genomic era

Seminars in Cancer Biology

Volumn 55, Issue , 2019, Pages 16-27

  Chen, Hui Zi ^a   Bonneville, Russell ^b   Roychowdhury, Sameek ^a  

^a THE OHIO STATE UNIVERSITY WEXNER MEDICAL CENTER   (United States)

^b OHIO STATE UNIVERSITY   (United States)

Author keywords

Actionable variants; Clinical trials; Genomics; Precision oncology; Targeted therapies

Indexed keywords

CIRCULATING TUMOR DNA; TUMOR MARKER;

CANCER PROGNOSIS; CLINICAL TRIAL (TOPIC); COPY NUMBER VARIATION; DNA METHYLATION; EPIGENETICS; GENE FUSION; GENETIC ANALYSIS; GENETIC ASSOCIATION; GENETIC VARIATION; GENOMICS; GERMLINE MUTATION; HETEROZYGOTE; HOMOLOGOUS RECOMBINATION; HUMAN; INDEL MUTATION; MALIGNANT NEOPLASM; MICROSATELLITE INSTABILITY; NEXT GENERATION SEQUENCING; PERSONALIZED MEDICINE; REVIEW; SINGLE NUCLEOTIDE POLYMORPHISM; TUMOR VOLUME; GENETICS; HIGH THROUGHPUT SEQUENCING; HUMAN GENOME; NEOPLASM; ONCOLOGY; TRENDS;

BIOMARKERS, TUMOR; GENOME, HUMAN; GENOMICS; HIGH-THROUGHPUT NUCLEOTIDE SEQUENCING; HUMANS; MEDICAL ONCOLOGY; NEOPLASMS; PRECISION MEDICINE;

EID: 85048771048     PISSN: 1044579X     EISSN: 10963650     Source Type: Journal    
DOI: 10.1016/j.semcancer.2018.05.009     Document Type: Review

References (143)

1. Venter, J.C., Smith, H.O., Adams, M.D., The sequence of the human genome. Clin. Chem. 61:9 (2015), 1207–1208.
2. Lander, E.S., Linton, L.M., Birren, B., Nusbaum, C., Zody, M.C., Baldwin, J., et al. Initial sequencing and analysis of the human genome. Nature 409:6822 (2001), 860–921.
3. Gerlinger, M., Rowan, A.J., Horswell, S., Math, M., Larkin, J., Endesfelder, D., et al. Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N. Engl. J. Med. 366:10 (2012), 883–892.
4. Gerlinger, M., Horswell, S., Larkin, J., Rowan, A.J., Salm, M.P., Varela, I., et al. Genomic architecture and evolution of clear cell renal cell carcinomas defined by multiregion sequencing. Nat. Genet. 46:3 (2014), 225–233.
5. Faltas, B.M., Prandi, D., Tagawa, S.T., Molina, A.M., Nanus, D.M., Sternberg, C., et al. Clonal evolution of chemotherapy-resistant urothelial carcinoma. Nat. Genet. 48:12 (2016), 1490–1499.
6. Carr, T.H., McEwen, R., Dougherty, B., Johnson, J.H., Dry, J.R., Lai, Z., et al. Defining actionable mutations for oncology therapeutic development. Nat. Rev. Cancer 16:5 (2016), 319–329.
7. Zehir, A., Benayed, R., Shah, R.H., Syed, A., Middha, S., Kim, H.R., et al. Mutational landscape of metastatic cancer revealed from prospective clinical sequencing of 10,000 patients. Nat. Med. 23:6 (2017), 703–713.
8. Sherry, S.T., Ward, M.H., Kholodov, M., Baker, J., Phan, L., Smigielski, E.M., et al. dbSNP: the NCBI database of genetic variation. Nucleic Acids Res. 29:1 (2001), 308–311.
9. Siepel, A., Bejerano, G., Pedersen, J.S., Hinrichs, A.S., Hou, M., Rosenbloom, K., et al. Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes. Genome Res. 15:8 (2005), 1034–1050.
10. Pollard, K.S., Hubisz, M.J., Rosenbloom, K.R., Siepel, A., Detection of nonneutral substitution rates on mammalian phylogenies. Genome Res. 20:1 (2010), 110–121.
11. Kumar, P., Henikoff, S., Ng, P.C., Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm. Nat. Protoc., 4, 2009, 1073.
12. Choi, Y., Sims, G.E., Murphy, S., Miller, J.R., Chan, A.P., Predicting the functional effect of amino acid substitutions and indels. PLoS One, 7(10), 2012, e46688.
13. Adzhubei, I.A., Schmidt, S., Peshkin, L., Ramensky, V.E., Gerasimova, A., Bork, P., et al. A method and server for predicting damaging missense mutations. Nat. Methods, 7, 2010, 248.
14. Shihab, H.A., Gough, J., Cooper, D.N., Stenson, P.D., Barker, G.L.A., Edwards, K.J., et al. Predicting the functional, molecular, and phenotypic consequences of amino acid substitutions using hidden Markov models. Hum. Mutat. 34:1 (2013), 57–65.
15. Kircher, M., Witten, D.M., Jain, P., O'Roak, B.J., Cooper, G.M., Shendure, J., A general framework for estimating the relative pathogenicity of human genetic variants. Nat. Genet., 46, 2014, 310.
16. Quang, D., Chen, Y., Xie, X., DANN: a deep learning approach for annotating the pathogenicity of genetic variants. Bioinformatics 31:5 (2015), 761–763.
17. Ioannidis, N.M., Rothstein, J.H., Pejaver, V., Middha, S., McDonnell, S.K., Baheti, S., et al. REVEL: an ensemble method for predicting the pathogenicity of rare missense variants. Am. J. Hum. Genet. 99:4 (2016), 877–885.
18. Martelotto, L.G., Ng, C.K.Y., De Filippo, M.R., Zhang, Y., Piscuoglio, S., Lim, R.S., et al. Benchmarking mutation effect prediction algorithms using functionally validated cancer-related missense mutations. Genome Biol., 15(10), 2014, 484.
19. Dong, C., Wei, P., Jian, X., Gibbs, R., Boerwinkle, E., Wang, K., et al. Comparison and integration of deleteriousness prediction methods for nonsynonymous SNVs in whole exome sequencing studies. Hum. Mol. Genet. 24:8 (2015), 2125–2137.
20. Beroukhim, R., Mermel, C.H., Porter, D., Wei, G., Raychaudhuri, S., Donovan, J., et al. The landscape of somatic copy-number alteration across human cancers. Nature 463:7283 (2010), 899–905.
21. Mishra, S., Whetstine, J.R., Different facets of copy number changes: permanent, transient, and adaptive. Mol. Cell. Biol. 36:7 (2016), 1050–1063.
22. Zack, T.I., Schumacher, S.E., Carter, S.L., Cherniack, A.D., Saksena, G., Tabak, B., et al. Pan-cancer patterns of somatic copy number alteration. Nat. Genet. 45:10 (2013), 1134–1140.
23. Weir, B.A., Woo, M.S., Getz, G., Perner, S., Ding, L., Beroukhim, R., et al. Characterizing the cancer genome in lung adenocarcinoma. Nature 450:7171 (2007), 893–898.
24. Kim, T.M., Xi, R., Luquette, L.J., Park, R.W., Johnson, M.D., Park, P.J., Functional genomic analysis of chromosomal aberrations in a compendium of 8000 cancer genomes. Genome Res. 23:2 (2013), 217–227.
25. Stephens, P.J., McBride, D.J., Lin, M.L., Varela, I., Pleasance, E.D., Simpson, J.T., et al. Complex landscapes of somatic rearrangement in human breast cancer genomes. Nature 462:7276 (2009), 1005–1010.
26. Harada, T., Chelala, C., Bhakta, V., Chaplin, T., Caulee, K., Baril, P., et al. Genome-wide DNA copy number analysis in pancreatic cancer using high-density single nucleotide polymorphism arrays. Oncogene 27:13 (2008), 1951–1960.
27. Mitelman, F., Johansson, B., Mertens, F., The impact of translocations and gene fusions on cancer causation. Nat. Rev. Cancer 7:4 (2007), 233–245.
28. Soda, M., Choi, Y.L., Enomoto, M., Takada, S., Yamashita, Y., Ishikawa, S., et al. Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature 448:7153 (2007), 561–566.
29. Vaishnavi, A., Capelletti, M., Le AT, Kako S., Butaney, M., Ercan, D., et al. Oncogenic and drug-sensitive NTRK1 rearrangements in lung cancer. Nat. Med. 19:11 (2013), 1469–1472.
30. 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. 18:3 (2012), 382–384.
31. Wu, Y.M., Su, F., Kalyana-Sundaram, S., Khazanov, N., Ateeq, B., Cao, X., et al. Identification of targetable FGFR Gene fusions in diverse cancers. Cancer Discov., 2013.
32. Takeuchi, K., Soda, M., Togashi, Y., Suzuki, R., Sakata, S., Hatano, S., et al. RET, ROS1 and ALK fusions in lung cancer. Nat. Med. 18:3 (2012), 378–381.
33. Bergethon, K., Shaw, A.T., Ou, S.H., Katayama, R., Lovly, C.M., McDonald, N.T., et al. ROS1 rearrangements define a unique molecular class of lung cancers. J. Clin. Oncol. 30:8 (2012), 863–870.
34. Palanisamy, N., Ateeq, B., Kalyana-Sundaram, S., Pflueger, D., Ramnarayanan, K., Shankar, S., et al. Rearrangements of the RAF kinase pathway in prostate cancer, gastric cancer and melanoma. Nat. Med. 16:7 (2010), 793–798.
35. Chmielecki, J., Hutchinson, K.E., Frampton, G.M., Chalmers, Z.R., Johnson, A., Shi, C., et al. Comprehensive genomic profiling of pancreatic acinar cell carcinomas identifies recurrent RAF fusions and frequent inactivation of DNA repair genes. Cancer Discov. 4:12 (2014), 1398–1405.
36. Maher, C.A., Palanisamy, N., Brenner, J.C., Cao, X., Kalyana-Sundaram, S., Luo, S., et al. Chimeric transcript discovery by paired-end transcriptome sequencing. Proc. Natl. Acad. Sci. U. S. A., 2009.
37. Maher, C.A., Kumar-Sinha, C., Cao, X., Kalyana-Sundaram, S., Han, B., Jing, X., et al. Transcriptome sequencing to detect gene fusions in cancer. Nature 458:7234 (2009), 97–101.
38. Stransky, N., Cerami, E., Schalm, S., Kim, J.L., Lengauer, C., The landscape of kinase fusions in cancer. Nat. Commun., 5, 2014, 4846.
39. Gao, Q., Liang, W.-W., Foltz, S.M., Mutharasu, G., Jayasinghe, R.G., Cao, S., et al. Driver fusions and their implications in the development and treatment of human cancers. Cell Rep. 23:1 (2018), 227–238 e3.
40. Levin, J.Z., Berger, M.F., Adiconis, X., Rogov, P., Melnikov, A., Fennell, T., et al. Targeted next-generation sequencing of a cancer transcriptome enhances detection of sequence variants and novel fusion transcripts. Genome Biol., 10(10), 2009, R115.
41. Reeser, J.W., Martin, D., Miya, J., Kautto, E.A., Lyon, E., Zhu, E., et al. Validation of a targeted RNA sequencing assay for kinase fusion detection in solid tumors. J. Mol. Diagn. 19:5 (2017), 682–696.
42. Zheng, Z., Liebers, M., Zhelyazkova, B., Cao, Y., Panditi, D., Lynch, K.D., et al. Anchored multiplex PCR for targeted next-generation sequencing. Nat. Med. 20:12 (2014), 1479–1484.
43. Stratton, M.R., Campbell, P.J., Futreal, P.A., The cancer genome. Nature 458:7239 (2009), 719–724.
44. Carbone, D.P., Reck, M., Paz-Ares, L., Creelan, B., Horn, L., Steins, M., et al. First-line nivolumab in stage IV or recurrent Non-small-cell lung cancer. N Engl. J. Med. 376:25 (2017), 2415–2426.
45. Yarchoan, M., Hopkins, A., Jaffee, E.M., Tumor mutational burden and response rate to PD-1 inhibition. N. Engl. J. Med. 377:25 (2017), 2500–2501.
46. Gibney, G.T., Weiner, L.M., Atkins, M.B., Predictive biomarkers for checkpoint inhibitor-based immunotherapy. Lancet Oncol. 17:12 (2016), e542–e551.
47. Rooney, M.S., Shukla, S.A., Wu, C.J., Getz, G., Hacohen, N., Molecular and genetic properties of tumors associated with local immune cytolytic activity. Cell 160:1-2 (2015), 48–61.
48. Rosenberg, J.E., Hoffman-Censits, J., Powles, T., van der Heijden, M.S., Balar, A.V., Necchi, A., et al. Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. Lancet 387:10031 (2016), 1909–1920.
49. Alexandrov, L.B., Nik-Zainal, S., Wedge, D.C., Aparicio, S.A., Behjati, S., Biankin, A.V., et al. Signatures of mutational processes in human cancer. Nature 500:7463 (2013), 415–421.
50. Weinhold, N., Jacobsen, A., Schultz, N., Sander, C., Lee, W., Genome-wide analysis of non-coding regulatory mutations in cancer. Nat. Genet. 46:11 (2014), 1160–1165.
51. Govindan, R., Ding, L., Griffith, M., Subramanian, J., Dees, N.D., Kanchi, K.L., et al. Genomic landscape of non-small cell lung cancer in smokers and never-smokers. Cell 150:6 (2012), 1121–1134.
52. Genomic classification of cutaneous melanoma. Cell 161:7 (2015), 1681–1696.
53. Comprehensive molecular characterization of urothelial bladder carcinoma. Nature 507:7492 (2014), 315–322.
54. Campbell, B.B., Light, N., Fabrizio, D., Zatzman, M., Fuligni, F., de Borja, R., et al. Comprehensive analysis of hypermutation in human cancer. Hum. Cancer Cell. 171:5 (2017), 1042–1056 e10.
55. Roberts, S.A., Lawrence, M.S., Klimczak, L.J., Grimm, S.A., Fargo, D., Stojanov, P., et al. An APOBEC cytidine deaminase mutagenesis pattern is widespread in human cancers. Nat. Genet. 45:9 (2013), 970–976.
56. Bouffet, E., Larouche, V., Campbell, B.B., Merico, D., de Borja, R., Aronson, M., et al. Immune checkpoint inhibition for hypermutant glioblastoma multiforme resulting from germline biallelic mismatch repair deficiency. J. Clin. Oncol. 34:19 (2016), 2206–2211.
57. Diaz, L.A., Jr, Le, DT. PD-1 blockade in tumors with mismatch-repair deficiency. N. Engl. J. Med., 373(20), 2015, 1979.
58. Johanns, T.M., Miller, C.A., Dorward, I.G., Tsien, C., Chang, E., Perry, A., et al. Immunogenomics of hypermutated glioblastoma: a patient with germline POLE deficiency treated with checkpoint blockade immunotherapy. Cancer Discov. 6:11 (2016), 1230–1236.
59. Le DT, Uram J.N., Wang, H., Bartlett, B.R., Kemberling, H., Eyring, A.D., et al. PD-1 blockade in tumors with mismatch-repair deficiency. N. Engl. J. Med. 372:26 (2015), 2509–2520.
60. Rizvi, N.A., Hellmann, M.D., Snyder, A., Kvistborg, P., Makarov, V., Havel, J.J., et al. Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science 348:6230 (2015), 124–128.
61. Santin, A.D., Bellone, S., Buza, N., Choi, J., Schwartz, P.E., Schlessinger, J., et al. Regression of chemotherapy-resistant polymerase epsilon (POLE) ultra-mutated and MSH6 hyper-mutated endometrial tumors with nivolumab. Clin. Cancer Res. 22:23 (2016), 5682–5687.
62. Snyder, A., Makarov, V., Merghoub, T., Yuan, J., Zaretsky, J.M., Desrichard, A., et al. Genetic basis for clinical response to CTLA-4 blockade in melanoma. N. Engl. J. Med. 371:23 (2014), 2189–2199.
63. Van Allen, E.M., Miao, D., Schilling, B., Shukla, S.A., Blank, C., Zimmer, L., et al. Genomic correlates of response to CTLA-4 blockade in metastatic melanoma. Science 350:6257 (2015), 207–211.
64. Hampel, H., Frankel, W.L., Martin, E., Arnold, M., Khanduja, K., Kuebler, P., et al. Screening for the lynch syndrome (hereditary nonpolyposis colorectal cancer). N. Engl. J. Med. 352:18 (2005), 1851–1860.
65. Lynch, H.T., Swartz, M., Lynch, J., Krush, A.J., A family study of adenocarcinoma of the colon and multiple primary cancer. Surg. Gynecol. Obstet. 134:5 (1972), 781–786.
66. Zighelboim, I., Goodfellow, P.J., Gao, F., Gibb, R.K., Powell, M.A., Rader, J.S., et al. Microsatellite instability and epigenetic inactivation of MLH1 and outcome of patients with endometrial carcinomas of the endometrioid type. J. Clin. Oncol. 25:15 (2007), 2042–2048.
67. Hampel, H., Frankel, W., Panescu, J., Lockman, J., Sotamaa, K., Fix, D., et al. Screening for lynch syndrome (hereditary nonpolyposis colorectal cancer) among endometrial cancer patients. Cancer Res. 66:15 (2006), 7810–7817.
68. Cancer Genome Atlas Research N, Comprehensive molecular characterization of gastric adenocarcinoma. Nature 513:7517 (2014), 202–209.
69. Pritchard, C.C., Morrissey, C., Kumar, A., Zhang, X., Smith, C., Coleman, I., et al. Complex MSH2 and MSH6 mutations in hypermutated microsatellite unstable advanced prostate cancer. Nat. Commun., 5, 2014, 4988.
70. Dudley, J.C., Lin, M.T., Le, D.T., Eshleman, J.R., Microsatellite instability as a biomarker for PD-1 blockade. Clin. Cancer Res. 22:4 (2016), 813–820.
71. Niu, B., Ye, K., Zhang, Q., Lu, C., Xie, M., McLellan, M.D., et al. MSIsensor: microsatellite instability detection using paired tumor-normal sequence data. Bioinformatics 30:7 (2014), 1015–1016.
72. Salipante, S.J., Scroggins, S.M., Hampel, H.L., Turner, E.H., Pritchard, C.C., Microsatellite instability detection by next generation sequencing. Clin. Chem. 60:9 (2014), 1192–1199.
73. Kautto, E.A., Bonneville, R., Miya, J., Yu, L., Krook, M.A., Reeser, J.W., et al. Performance evaluation for rapid detection of pan-cancer microsatellite instability with MANTIS. Oncotarget 8:5 (2017), 7452–7463.
74. Hempelmann, J.A., Scroggins, S.M., Pritchard, C.C., Salipante, S.J., MSIplus: integrated colorectal cancer molecular testing by next-generation sequencing. J. Mol. Diagn., 2015.
75. Pritchard, C.C., Smith, C., Salipante, S.J., Lee, M.K., Thornton, A.M., Nord, A.S., et al. ColoSeq provides comprehensive lynch and polyposis syndrome mutational analysis using massively parallel sequencing. J. Mol. Diagn. 14:4 (2012), 357–366.
76. Bonneville, R., Krook, M.A., Kautto, E.A., Miya, J., Wing, M.R., Chen, H.-Z., et al. Landscape of microsatellite instability across 39 cancer types. JCO Precis. Oncol.(1), 2017, 1–15.
77. Middha, S., Zhang, L., Nafa, K., Jayakumaran, G., Wong, D., Kim, H.R., et al. Reliable pan-cancer microsatellite instability assessment by using targeted next-generation sequencing data. JCO Precis. Oncol.(1), 2017, 1–17.
78. Hause, R.J., Pritchard, C.C., Shendure, J., Salipante, S.J., Classification and characterization of microsatellite instability across 18 cancer types. Nat. Med. 22:11 (2016), 1342–1350.
79. Hanahan, D., Weinberg, R.A., Hallmarks of cancer: the next generation. Cell 144:5 (2011), 646–674.
80. Hahn, W.C., Weinberg, R.A., Rules for making human tumor cells. N. Engl. J. Med. 347:20 (2002), 1593–1603.
81. Feinberg, A.P., Ohlsson, R., Henikoff, S., The epigenetic progenitor origin of human cancer. Nat. Rev. Genet. 7:1 (2006), 21–33.
82. You, J.S., Jones, P.A., Cancer genetics and epigenetics: two sides of the same coin?. Cancer Cell. 22:1 (2012), 9–20.
83. Shen, L., Choi, I., Nestler, E.J., Won, K.J., Human transcriptome and chromatin modifications: an ENCODE perspective. Genomics Inf. 11:2 (2013), 60–67.
84. Strahl, B.D., Allis, C.D., The language of covalent histone modifications. Nature 403:6765 (2000), 41–45.
85. Jenuwein, T., Allis, C.D., Translating the histone code. Science 293:5532 (2001), 1074–1080.
86. Ernst, J., Kellis, M., Discovery and characterization of chromatin states for systematic annotation of the human genome. Nat. Biotechnol., 28, 2010, 817.
87. Nebbioso, A., Carafa, V., Benedetti, R., Altucci, L., Trials with’ epigenetic’ drugs: an update. Mol. Oncol. 6:6 (2012), 657–682.
88. Cech, T.R., Steitz, J.A., The noncoding RNA revolution-trashing old rules to forge new ones. Cell 157:1 (2014), 77–94.
89. Rupaimoole, R., Slack, F.J., MicroRNA therapeutics: towards a new era for the management of cancer and other diseases. Nat. Rev. Drug Discov. 16:3 (2017), 203–222.
90. Jones, P.A., Functions of DNA methylation: islands, start sites, gene bodies and beyond. Nat. Rev. Genet. 13:7 (2012), 484–492.
91. Shen, L., Kondo, Y., Rosner, G.L., Xiao, L., Hernandez, N.S., Vilaythong, J., et al. MGMT promoter methylation and field defect in sporadic colorectal cancer. J. Natl. Cancer Inst. 97:18 (2005), 1330–1338.
92. Yang, F., Gong, Q., Shi, W., Zou, Y., Shi, J., Wei, F., et al. Aberrant DNA methylation of acute myeloid leukemia and colorectal cancer in a Chinese pedigree with a MLL3 germline mutation. Tumour Biol. 37:9 (2016), 12609–12618.
93. Lu, R., Wang, P., Parton, T., Zhou, Y., Chrysovergis, K., Rockowitz, S., et al. Epigenetic perturbations by Arg882-mutated DNMT3A potentiate aberrant stem cell gene-expression program and acute leukemia development. Cancer Cell 30:1 (2016), 92–107.
94. Goll, M.G., Bestor, T.H., Eukaryotic cytosine methyltransferases. Annu. Rev. Biochem. 74 (2005), 481–514.
95. Landau, D.A., Clement, K., Ziller, M.J., Boyle, P., Fan, J., Gu, H., et al. Locally disordered methylation forms the basis of intratumor methylome variation in chronic lymphocytic leukemia. Cancer Cell. 26:6 (2014), 813–825.
96. Hansen, K.D., Timp, W., Bravo, H.C., Sabunciyan, S., Langmead, B., McDonald, O.G., et al. Increased methylation variation in epigenetic domains across cancer types. Nat. Genet. 43:8 (2011), 768–775.
97. Lord, C.J., Ashworth, A., BRCAness revisited. Nat. Rev. Cancer 16:2 (2016), 110–120.
98. Lord, C.J., Ashworth, A., The DNA damage response and cancer therapy. Nature, 481, 2012, 287.
99. Tutt, A., Robson, M., Garber, J.E., Domchek, S.M., Audeh, M.W., Weitzel, J.N., et al. Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and advanced breast cancer: a proof-of-concept trial. Lancet 376:9737 (2010), 235–244.
100. Audeh, M.W., Carmichael, J., Penson, R.T., Friedlander, M., Powell, B., Bell-McGuinn, K.M., et al. Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer: a proof-of-concept trial. Lancet 376:9737 (2010), 245–251.
101. Ledermann, J., Harter, P., Gourley, C., Friedlander, M., Vergote, I., Rustin, G., et al. Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer. N. Engl. J. Med. 366:15 (2012), 1382–1392.
102. Mateo, J., Carreira, S., Sandhu, S., Miranda, S., Mossop, H., Perez-Lopez, R., et al. DNA-repair defects and olaparib in metastatic prostate cancer. N. Engl. J. Med. 373:18 (2015), 1697–1708.
103. Alexandrov, L.B., Nik-Zainal, S., Siu, H.C., Leung, S.Y., Stratton, M.R., A mutational signature in gastric cancer suggests therapeutic strategies. Nat. Commun., 6, 2015, 8683.
104. Connor, A.A., Denroche, R.E., Jang, G.H., Timms, L., Kalimuthu, S.N., Selander, I., et al. Association of distinct mutational signatures with correlates of increased immune activity in pancreatic ductal adenocarcinoma. JAMA Oncol. 3:6 (2017), 774–783.
105. Davies, H., Glodzik, D., Morganella, S., Yates, L.R., Staaf, J., Zou, X., et al. HRDetect is a predictor of BRCA1 and BRCA2 deficiency based on mutational signatures. Nat. Med. 23:4 (2017), 517–525.
106. Polak, P., Kim, J., Braunstein, L.Z., Karlic, R., Haradhavala, N.J., Tiao, G., et al. A mutational signature reveals alterations underlying deficient homologous recombination repair in breast cancer. Nat. Genet., 2017.
107. Alexandrov, L.B., Nik-Zainal, S., Wedge, D.C., Aparicio, S.A., Behjati, S., Biankin, A.V., et al. Signatures of mutational processes in human cancer. Nature 500:7463 (2013), 415–421.
108. Konstantinopoulos, P.A., Ceccaldi, R., Shapiro, G.I., D'Andrea, A.D., Homologous recombination deficiency: exploiting the fundamental vulnerability of ovarian cancer. Cancer Discov. 5:11 (2015), 1137–1154.
109. Swisher, E.M., Lin, K.K., Oza, A.M., Scott, C.L., Giordano, H., Sun, J., et al. Rucaparib in relapsed, platinum-sensitive high-grade ovarian carcinoma (ARIEL2 part 1): an international, multicentre, open-label, phase 2 trial. Lancet Oncol. 18:1 (2017), 75–87.
110. Yao, Z., Yaeger, R., Rodrik-Outmezguine, V.S., Tao, A., Torres, N.M., Chang, M.T., et al. Tumours with class 3 BRAF mutants are sensitive to the inhibition of activated RAS. Nature 548:7666 (2017), 234–238.
111. Klempner, S.J., Bordoni, R., Gowen, K., Kaplan, H., Stephens, P.J., Ou, S.H., et al. Identification of BRAF kinase domain duplications across multiple tumor types and response to RAF inhibitor therapy. JAMA Oncol. 2:2 (2016), 272–274.
112. Ross, J.S., Wang, K., Chmielecki, J., Gay, L., Johnson, A., Chudnovsky, J., et al. The distribution of BRAF gene fusions in solid tumors and response to targeted therapy. Int. J. Cancer 138:4 (2016), 881–890.
113. ECOG-ACRIN Cancer Research Group: NCI-MATCH/EAY 131 Interim Analysis, 2016.
114. Le Tourneau, C., Delord, J.P., Goncalves, A., Gavoille, C., Dubot, C., Isambert, N., et al. Molecularly targeted therapy based on tumour molecular profiling versus conventional therapy for advanced cancer (SHIVA): a multicentre, open-label, proof-of-concept, randomised, controlled phase 2 trial. Lancet Oncol. 16:13 (2015), 1324–1334.
115. Peguero, J.A., Knost, J.A., Bauer, T.M., Taylor, M.H., Braiteh, F.S., Eder, J.P., et al. Successful implementation of a novel trial model: the signature program. J. Clin. Oncol., 33(15_suppl), 2015, 106-.
116. Ritter, D.I., Roychowdhury, S., Roy, A., Rao, S., Landrum, M.J., Sonkin, D., et al. Somatic cancer variant curation and harmonization through consensus minimum variant level data. Genome Med., 8(1), 2016, 117.
117. Griffith, M., Spies, N.C., Krysiak, K., McMichael, J.F., Coffman, A.C., Danos, A.M., et al. CIViC is a community knowledgebase for expert crowdsourcing the clinical interpretation of variants in cancer. Nat. Genet. 49:2 (2017), 170–174.
118. Damodaran, S., Miya, J., Kautto, E., Zhu, E., Samorodnitsky, E., Datta, J., et al. cancer driver Log (CanDL): catalog of potentially actionable cancer mutations. J. Mol. Diagn. 17:5 (2015), 554–559.
119. Chakravarty, D., Gao, J., Phillips, S.M., Kundra, R., Zhang, H., Wang, J., et al. OncoKB: a precision oncology knowledge Base. JCO Precis. Oncol., 2017, 2017.
120. Geifman, N., Haviv, I., Kurzrock, R., Rubin, E., Promoting precision cancer medicine through a Community-driven knowledgebase. J. Pers. Med. 4:4 (2014), 475–488.
121. Ritter, D.I., Roychowdhury, S., Roy, A., Rao, S., Landrum, M.J., Sonkin, D., et al. Somatic cancer variant curation and harmonization through consensus minimum variant level data. Genome Med., 8(1), 2016, 117.
122. Renfro, L.A., Sargent, D.J., Statistical controversies in clinical research: basket trials, umbrella trials, and other master protocols: a review and examples. Ann. Oncol. 28:1 (2017), 34–43.
123. Hyman, D.M., Puzanov, I., Subbiah, V., Faris, J.E., Chau, I., Blay, J.Y., et al. Vemurafenib in multiple nonmelanoma cancers with BRAF V600 mutations. N. Engl. J. Med. 373:8 (2015), 726–736.
124. Schoffski, P., Wozniak, A., Escudier, B., Rutkowski, P., Anthoney, A., Bauer, S., et al. Crizotinib achieves long-lasting disease control in advanced papillary renal-cell carcinoma type 1 patients with MET mutations or amplification. EORTC 90101 CREATE trial. Eur J. Cancer 87 (2017), 147–163.
125. Schoffski, P., Wozniak, A., Kasper, B., Aamdal, S., Leahy, M.G., Rutkowski, P., et al. Activity and safety of crizotinib in patients with alveolar soft part sarcoma with rearrangement of TFE3. European organization for research and treatment of cancer (EORTC) phase 2 trial 90101 “CREATE”. Ann. Oncol., 2017.
126. Schoffski, P., Wozniak, A., Stacchiotti, S., Rutkowski, P., Blay, J.Y., Lindner, L.H., et al. Activity and safety of crizotinib in patients with advanced clear-cell sarcoma with MET alterations: European organization for research and treatment of cancer phase II trial 90101’ CREATE’. Ann. Oncol. 28:12 (2017), 3000–3008.
127. Conley, B.A., Doroshow, J.H., Molecular analysis for therapy choice: NCI MATCH. Semin. Oncol. 41:3 (2014), 297–299.
128. Bedard, P.L., Hansen, A.R., Ratain, M.J., Siu, L.L., Tumour heterogeneity in the clinic. Nature, 501, 2013, 355.
129. Turajlic, S., Swanton, C., Metastasis as an evolutionary process. Science, 352(6282), 2016, 169.
130. Jonsson, V.D., Blakely, C.M., Lin, L., Asthana, S., Matni, N., Olivas, V., et al. Novel computational method for predicting polytherapy switching strategies to overcome tumor heterogeneity and evolution. Sci. Rep., 7, 2017, 44206.
131. McGranahan, N., Swanton, C., Clonal heterogeneity and tumor evolution: past, present, and the future. Cell 168:4 (2018), 613–628.
132. Juric, D., Castel, P., Griffith, M., Griffith, O.L., Won, H.H., Ellis, H., et al. Convergent loss of PTEN leads to clinical resistance to a PI(3)kalpha inhibitor. Nature 518:7538 (2015), 240–244.
133. Merlo, L.M.F., Pepper, J.W., Reid, B.J., Maley, C.C., Cancer as an evolutionary and ecological process. Nat. Rev. Cancer, 6, 2006, 924.
134. Jiao, W., Vembu, S., Deshwar, A.G., Stein, L., Morris, Q., Inferring clonal evolution of tumors from single nucleotide somatic mutations. BMC Bioinform., 15(1), 2014, 35.
135. Jiang, Y., Qiu, Y., Minn, A.J., Zhang, N.R., Assessing intratumor heterogeneity and tracking longitudinal and spatial clonal evolutionary history by next-generation sequencing. Proc. Natl. Acad. Sci. U. S. A. 113:37 (2016), E5528–37.
136. Navin, N.E., Cancer genomics: one cell at a time. Genome Biol., 15(8), 2014, 452.
137. Wang, Y., Waters, J., Leung, M.L., Unruh, A., Roh, W., Shi, X., et al. Clonal evolution in breast cancer revealed by single nucleus genome sequencing. Nature, 512, 2014, 155.
138. Tolcher, A.W., Peng, W., Calvo, E., Rational approaches for combination therapy strategies targeting the MAP kinase pathway in solid tumors. Mol. Cancer Ther. 17:1 (2018), 3–16.
139. Merker, J.D., Oxnard, G.R., Compton, C., Diehn, M., Hurley, P., Lazar, A.J., et al. Circulating tumor DNA analysis in patients with cancer: American society of clinical oncology and College of American pathologists joint review. J. Clin. Oncol., 2018, Jco2017768671.
140. Stroun, M., Maurice, P., Vasioukhin, V., Lyautey, J., Lederrey, C., Lefort, F., et al. The origin and mechanism of circulating DNA. Ann. N. Y. Acad. Sci. 906 (2000), 161–168.
141. Esposito, A., Criscitiello, C., Locatelli, M., Milano, M., Curigliano, G., Liquid biopsies for solid tumors: understanding tumor heterogeneity and real time monitoring of early resistance to targeted therapies. Pharmacol. Ther. 157 (2016), 120–124.
142. Siravegna, G., Marsoni, S., Siena, S., Bardelli, A., Integrating liquid biopsies into the management of cancer. Nat. Rev. Clin. Oncol. 14:9 (2017), 531–548.
143. Simon, R., Optimal two-stage designs for phase II clinical trials. Control Clin. Trials 10:1 (1989), 1–10 PubMed PMID: 2702835.