Molecular analysis of cell-free circulating DNA for the diagnosis of somatic mutations associated with resistance to tyrosine kinase inhibitors in non-small-cell lung cancer

Expert Review of Molecular Diagnostics

Volumn 14, Issue 4, 2014, Pages 453-468

  Del Re, Marzia ^a   Vasile, Enrico ^a   Falcone, Alfredo ^a   Danesi, Romano ^a   Petrini, Iacopo ^a  

^a UNIVERSITY OF PISA   (Italy)

Author keywords

acquired resistance; ALK; circulating cell free tumor DNA; EGFR; non small cell lung cancer; pharmacologic inhibitors

Indexed keywords

ANAPLASTIC LYMPHOMA KINASE; B RAF KINASE; CRIZOTINIB; DISCOIDIN; DISCOIDIN DOMAIN CONTAINING RECEPTOR 2; DNA; EPIDERMAL GROWTH FACTOR RECEPTOR; EPIDERMAL GROWTH FACTOR RECEPTOR 2; ERLOTINIB; FIBROBLAST GROWTH FACTOR RECEPTOR 1; GEFITINIB; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B; PROTEIN RET; PROTEIN TYROSINE KINASE INHIBITOR; UNCLASSIFIED DRUG; ANTINEOPLASTIC AGENT; EGFR PROTEIN, HUMAN; PROTEIN KINASE INHIBITOR;

CELL FREE SYSTEM; CIRCULATING TUMOR CELL; CLINICAL TRIAL (TOPIC); DNA DETERMINATION; DNA SEQUENCE; GENETIC ASSOCIATION; GENOTYPE; HUMAN; LUNG NON SMALL CELL CANCER; MASS SPECTROMETRY; MOLECULAR DIAGNOSIS; NEXT GENERATION SEQUENCING; PROTEIN TARGETING; PYROSEQUENCING; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; REVIEW; SOMATIC MUTATION; ANIMAL; ANTAGONISTS AND INHIBITORS; BLOOD; CARCINOMA, NON-SMALL-CELL LUNG; DRUG RESISTANCE; GENETICS; LUNG NEOPLASMS; MUTATION; NUCLEOTIDE SEQUENCE;

ANIMALS; ANTINEOPLASTIC AGENTS; CARCINOMA, NON-SMALL-CELL LUNG; DNA; DNA MUTATIONAL ANALYSIS; DRUG RESISTANCE, NEOPLASM; HUMANS; LUNG NEOPLASMS; MUTATION; PROTEIN KINASE INHIBITORS; RECEPTOR, EPIDERMAL GROWTH FACTOR;

EID: 84898998368     PISSN: 14737159     EISSN: 17448352     Source Type: Journal    
DOI: 10.1586/14737159.2014.908120     Document Type: Review

References (114)

1. Kozower BD, Larner JM, Detterbeck FC, Jones DR. Special treatment issues in non-small cell lung cancer: diagnosis and management of lung cancer, 3rd edition: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2013;143(5 Suppl):e369S-99S
2. Imielinski M, Berger AH, Hammerman PS, et al. Mapping the hallmarks of lung adenocarcinoma with massively parallel sequencing. Cell 2012;150(6):1107-20
3. Cancer Genome Atlas Research Network. Comprehensive genomic characterization of squamous cell lung cancers. Nature 2012; 489(7417):519-25
4. Oxnard GR, Binder A, Janne PA. New targetable oncogenes in non-small-cell lung cancer. J Clin Oncol 2013;31(8):1097-104
5. Rosell R, Carcereny E, Gervais R, et al. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol 2012;13(3): 239-46
6. Zhou C, Wu YL, Chen G, et al. Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study. Lancet Oncol 2011;12(8):735-42
7. Mitsudomi T, Morita S, Yatabe Y, et al. Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial. Lancet Oncol 2010;11(2):121-8
8. Maemondo M, Inoue A, Kobayashi K, et al. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med 2010;362(25):2380-8
9. Goto K, Ichinose Y, Ohe Y, et al. Epidermal growth factor receptor mutation status in circulating free DNA in serum: from IPASS, a phase III study of gefitinib or carboplatin/paclitaxel in non-small cell lung cancer. J Thorac Oncol 2012;7(1): 115-21
10. Han JY, Park K, Kim SW, et al. First- SIGNAL: first-line single-agent iressa versus gemcitabine and cisplatin trial in never-smokers with adenocarcinoma of the lung. J Clin Oncol 2012;30(10):1122-8
11. Sequist LV, Yang JC, Yamamoto N, et al. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol 2013;31(27):3327-34
12. Wu YL, Zhou C, Hu C, et al. LUX-Lung 6: a randomized, open-label, phase III study of afatinib (A) versus gemcitabine/cisplatin (GC) as first-line treatment for Asian patients (pts) with EGFR mutation-positive (EGFR M+) advanced adenocarcinoma of the lung. J Clin Oncol 2013;31(Suppl): abstract 8016
13. Cappuzzo F, Ciuleanu T, Stelmakh L, et al. Erlotinib as maintenance treatment in advanced non-small-cell lung cancer: a multicentre, randomised, placebo-controlled phase 3 study. Lancet Oncol 2010;11(6):521-9
14. Bezjak A, Tu D, Seymour L, et al. Symptom improvement in lung cancer patients treated with erlotinib: quality of life analysis of the National Cancer Institute of Canada Clinical Trials Group Study BR.21. J Clin Oncol 2006;24(24):3831-7 (Pubitemid 46630729
15. Shaw AT, Engelman JA. ALK in lung cancer: past, present, and future. J Clin Oncol 2013;31(8):1105-11
16. Camidge DR, Bang YJ, Kwak EL, et al. Activity and safety of crizotinib in patients with ALK-positive non-small-cell lung cancer: updated results from a phase 1 study. Lancet Oncol 2012;13(10): 1011-19
17. Shaw AT, Kim DW, Nakagawa K, et al. Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N Engl J Med 2013;368(25):2385-94
18. Bergethon K, Shaw AT, Ou SH, et al. ROS1 rearrangements define a unique molecular class of lung cancers. J Clin Oncol 2012;30(8):863-70
19. Heinmoller P, Gross C, Beyser K, et al. HER2 status in non-small cell lung cancer: results from patient screening for enrollment to a phase II study of herceptin. Clin Cancer Res 2003;9(14):5238-43
20. Langer CJ, Stephenson P, Thor A, et al. Trastuzumab in the treatment of advanced non-small-cell lung cancer: is there a role? Focus on Eastern Cooperative Oncology Group study 2598. J Clin Oncol 2004; 22(7):1180-7 (Pubitemid 41079829
21. Ross HJ, Blumenschein GR Jr, Aisner J, et al. Randomized phase II multicenter trial of two schedules of lapatinib as first- or second-line monotherapy in patients with advanced or metastatic non-small cell lung cancer. Clin Cancer Res 2010;16(6): 1938-49
22. Arcila ME, Chaft JE, Nafa K, et al. Prevalence, clinicopathologic associations, and molecular spectrum of ERBB2 (HER2) tyrosine kinase mutations in lung adenocarcinomas. Clin Cancer Res 2012; 18(18):4910-18
23. Mazieres J, Peters S, Lepage B, et al. Lung cancer that harbors an HER2 mutation: epidemiologic characteristics and therapeutic perspectives. J Clin Oncol 2013;31(16): 1997-2003
24. Kris M, Goldberg Z, Janne PA, et al. Dacomitinib (PF-00299804), an irreversible PAN-HER tyrosine kinase inhibitor (TKI), for first-line treatment of EGFR-mutant or HER2-mutant or -amplified lung cancers. Ann Oncol 2012;23(Suppl 9):abstract 12280
25. Gandhi L, Bahleda R, Cleary JM, et al. Two-dimensional phase I study of neratinib (NER) combined with temsirolimus (TEM) in patients (Pts) with solid tumors. J Clin Oncol 2011;(Suppl):abstract 3027
26. Marchetti A, Felicioni L, Malatesta S, et al. Clinical features and outcome of patients with non-small-cell lung cancer harboring BRAF mutations. J Clin Oncol 2011; 29(26):3574-9
27. Gautschi O, Pauli C, Strobel K, et al. A patient with BRAF V600E lung adenocarcinoma responding to vemurafenib. J Thorac Oncol 2012;7(10):e23-4
28. Planchard D, Mazieres J, Riely GJ, et al. Interim results of phase II study BRF113928 of dabrafenib in BRAF V600E mutation-positive non-small cell lung cancer (NSCLC) patients. J Clin Oncol 2013;31(Suppl):abstract 8009
29. Yang H, Higgins B, Kolinsky K, et al. RG7204 (PLX4032), a selective BRAFV600E inhibitor, displays potent antitumor activity in preclinical melanoma models. Cancer Res 2010;70(13):5518-27
30. Takeuchi K, Soda M, Togashi Y, et al. RET, ROS1 and ALK fusions in lung cancer. Nat Med 2012;18(3):378-81
31. Lipson D, Capelletti M, Yelensky R, et al. Identification of new ALK and RET gene fusions from colorectal and lung cancer biopsies. Nat Med 2012;18(3): 382-4
32. Gautschi O, Zander T, Keller FA, et al. A patient with lung adenocarcinoma and RET fusion treated with vandetanib. Thorac Oncol 2013;8(5):e43-4
33. Platt A, Elvin P, Morten J, et al. Retrospective evaluation of RET biomarker status and outcome to vandetanib in four phase III randomized NSCLC trials. J Clin Oncol 2013;31(Suppl):abstract 8045
34. Drilon A, Wang L, Hasanovic A, et al. Response to cabozantinib in patients with RET fusion-positive lung adenocarcinomas. Cancer Discov 2013;3(6):630-5
35. Yamamoto H, Shigematsu H, Nomura M, et al. PIK3CA mutations and copy number gains in human lung cancers. Cancer Res 2008;68(17):6913-21
36. Ludovini V, Bianconi F, Pistola L, et al. Phosphoinositide-3-kinase catalytic alpha and KRAS mutations are important predictors of resistance to therapy with epidermal growth factor receptor tyrosine kinase inhibitors in patients with advanced non-small cell lung cancer. J Thorac Oncol 2011;6(4):707-15
37. Weiss J, Sos ML, Seidel D, et al. Frequent and focal FGFR1 amplification associates with therapeutically tractable FGFR1 dependency in squamous cell lung cancer. Sci Transl Med 2010;2(62):62ra93
38. Hammerman PS, Sos ML, Ramos AH, et al. Mutations in the DDR2 kinase gene identify a novel therapeutic target in squamous cell lung cancer. Cancer Discov 2011;1(1):78-89
39. Day E, Waters B, Spiegel K, et al. Inhibition of collagen-induced discoidin domain receptor 1 and 2 activation by imatinib, nilotinib and dasatinib. Eur J Pharmacol 2008;599(1-3):44-53
40. Johnson FM, Bekele BN, Feng L, et al. Phase II study of dasatinib in patients with advanced non-small-cell lung cancer. J Clin Oncol 2010;28(30):4609-15
41. Haura EB, Tanvetyanon T, Chiappori A, et al. Phase I/II study of the Src inhibitor dasatinib in combination with erlotinib in advanced non-small-cell lung cancer. J Clin Oncol 2010;28(8):1387-94
42. Gainor JF, Shaw AT. Emerging paradigms in the development of resistance to tyrosine kinase inhibitors in lung cancer. J Clin Oncol 2013;31(31):3987-96
43. Pao W, Miller VA, Politi KA, et al. Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain. PLoS Med 2005;2(3):e73
44. Bean J, Brennan C, Shih JY, et al. MET amplification occurs with or without T790M mutations in EGFR mutant lung tumors with acquired resistance to gefitinib or erlotinib. Proc Natl Acad Sci USA 2007; 104(52):20932-7
45. Takezawa K, Pirazzoli V, Arcila ME, et al. HER2 amplification: a potential mechanism of acquired resistance to EGFR inhibition in EGFR-mutant lung cancers that lack the second-site EGFRT790M mutation. Cancer Discov 2012;2(10):922-33
46. Sequist LV, Waltman BA, Dias-Santagata D, et al. Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors. Sci Transl Med 2011;3(75):75ra26
47. Ohashi K, Sequist LV, Arcila ME, et al. Lung cancers with acquired resistance to EGFR inhibitors occasionally harbor BRAF gene mutations but lack mutations in KRAS, NRAS, or MEK1. Proc Natl Acad Sci USA 2012;109(31):E2127-33
48. Li D, Shimamura T, Ji H, et al. Bronchial and peripheral murine lung carcinomas induced by T790M-L858R mutant EGFR respond to HKI-272 and rapamycin combination therapy. Cancer Cell 2007; 12(1):81-93 (Pubitemid 47001787
49. Yun CH, Mengwasser KE, Toms AV, et al. The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATP. Proc Natl Acad Sci USA 2008;105(6):2070-5 (Pubitemid 351439466
50. Godin-Heymann N, Bryant I, Rivera MN, et al. Oncogenic activity of epidermal growth factor receptor kinase mutant alleles is enhanced by the T790M drug resistance mutation. Cancer Res 2007;67(15):7319-26 (Pubitemid 47206561
51. Costa DB, Halmos B, Kumar A, et al. BIM mediates EGFR tyrosine kinase inhibitor-induced apoptosis in lung cancers with oncogenic EGFR mutations. PLoS Med 2007;4(10):1669-79.discussion 1680
52. Balak MN, Gong Y, Riely GJ, et al. Novel D761Y and common secondary T790M mutations in epidermal growth factor receptor-mutant lung adenocarcinomas with acquired resistance to kinase inhibitors. Clin Cancer Res 2006;12(21):6494-501 (Pubitemid 44799723
53. Bean J, Riely GJ, Balak M, et al. Acquired resistance to epidermal growth factor receptor kinase inhibitors associated with a novel T854A mutation in a patient with EGFR-mutant lung adenocarcinoma. Clin Cancer Res 2008;14(22):7519-25
54. Engelman JA, Zejnullahu K, Mitsudomi T, et al. MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science 2007;316(5827): 1039-43 (Pubitemid 46799492
55. Yano S, Wang W, Li Q, et al. Hepatocyte growth factor induces gefitinib resistance of lung adenocarcinoma with epidermal growth factor receptor-activating mutations. Cancer Res 2008;68(22):9479-87
56. Turke AB, Zejnullahu K, Wu YL, et al. Preexistence and clonal selection of MET amplification in EGFR mutant NSCLC. Cancer Cell 2010;17(1):77-88
57. Bivona T, Gianikopoulos P, Costa C, et al. Integrated genomic analysis by whole exome and transcriptome sequencing of tumor samples from EGFR-mutant non-small-cell lung cancer (NSCLC) patients with acquired resistance to erlotinib. J Thorac Oncol I 2013;8(Suppl 2):abstract MO21.05
58. Uramoto H, Iwata T, Onitsuka T, et al. Epithelial-mesenchymal transition in EGFR-TKI acquired resistant lung adenocarcinoma. Anticancer Res 2010; 30(7):2513-17
59. Chung JH, Rho JK, Xu X, et al. Clinical and molecular evidences of epithelial to mesenchymal transition in acquired resistance to EGFR-TKIs. Lung Cancer 2011;73(2):176-82
60. Thomson S, Buck E, Petti F, et al. Epithelial to mesenchymal transition is a determinant of sensitivity of non-small-cell lung carcinoma cell lines and xenografts to epidermal growth factor receptor inhibition. Cancer Res 2005;65(20):9455-62 (Pubitemid 41508014
61. Zhang Z, Lee JC, Lin L, et al. Activation of the AXL kinase causes resistance to EGFR-targeted therapy in lung cancer. Nat Genet 2012;44(8):852-60
62. Yu HA, Arcila ME, Rekhtman N, et al. Analysis of tumor specimens at the time of acquired resistance to EGFR-TKI therapy in 155 patients with EGFR-mutant lung cancers. Clin Cancer Res 2013;19(8):2240-7
63. Kwak EL, Sordella R, Bell DW, et al. Irreversible inhibitors of the EGF receptor may circumvent acquired resistance to gefitinib. Proc Natl Acad Sci USA 2005; 102(21):7665-70
64. Regales L, Gong Y, Shen R, et al. Dual targeting of EGFR can overcome a major drug resistance mutation in mouse models of EGFR mutant lung cancer. J Clin Invest 2009;119(10):3000-10
65. Miller VA, Hirsh V, Cadranel J, et al. Afatinib versus placebo for patients with advanced, metastatic non-small-cell lung cancer after failure of erlotinib, gefitinib, or both, and one or two lines of chemotherapy (LUX-Lung 1): a phase 2b/3 randomised trial. Lancet Oncol 2012;13(5):528-38
66. Janjigian YY, Smit EF, Horn L. Activity of afatinib/cetuximab in patients (pts) with EGFR mutant non-small cell lung cancer (NSCLC) and acquired resistance (AR) to EGFR inhibitors. Ann Oncol 2012; 23(Suppl 9):abstract 12270
67. Sequist LV, Besse B, Lynch TJ, et al. Neratinib, an irreversible pan-ErbB receptor tyrosine kinase inhibitor: results of a phase II trial in patients with advanced non-small-cell lung cancer. J Clin Oncol 2010;28(18):3076-83
68. Soria J, Sequist LV, Gadgeel S, et al. First-In-Human Evaluation of CO-1686, an Irreversible, Highly, Selective Tyrosine Kinase Inhibitor of Mutations of EGFR (Activating and T790M). J Thorac Oncol 2013;8(Suppl 2):abstract O03.06
69. Ranson M, Pao W, Kim D, et al. AZD9291: an irreversible, potent and selective tyrosine kinase inhibitor (TKI) of activating (EGFRm+) and resistance (T790M) mutations in advanced NSCLC. J Thorac Oncol 2013;8(Supp12):abstract MO21.12
70. Spigel DR, Ervin TJ, Ramlau RA, et al. Randomized phase II trial of onartuzumab in combination with erlotinib in patients with advanced non-small-cell lung cancer. Clin Oncol 2013;31(32):4105-14
71. Sequist LV, von Pawel J, Garmey EG, et al. Randomized phase II study of erlotinib plus tivantinib versus erlotinib plus placebo in previously treated non-small-cell lung cancer. Clin Oncol 2011;29(24):3307-15
72. Scagliotti GV, Novello S, von Pawel J. The emerging role of MET/HGF inhibitors in oncology. Cancer Treat Rev 2013;39(7): 793-801
73. Wakelee HA, Gettinger SN, Engelman JA, et al. A phase Ib/II study of XL184 (BMS 907351) with and without erlotinib (E) in patients (pts) with non-small cell lung cancer (NSCLC). J Clin Oncol 2010; 28(Suppl):abstract 3017
74. Ou SH, Kwak EL, Siwak-Tapp C, et al. Activity of crizotinib (PF02341066), a dual mesenchymal-epithelial transition (MET) and anaplastic lymphoma kinase (ALK) inhibitor, in a non-small cell lung cancer patient with de novo MET amplification. J Thorac 2011;6(5):942-6
75. Mao M, Tian F, Mariadason JM, et al. Resistance to BRAF inhibition in BRAF-mutant colon cancer can be overcome with PI3K inhibition or demethylating agents. Clin Cancer Res 2013;19(3):657-67
76. Riely GJ, Kris MG, Zhao B, et al. Prospective assessment of discontinuation and reinitiation of erlotinib or gefitinib in patients with acquired resistance to erlotinib or gefitinib followed by the addition of everolimus. Clin Cancer Res 2007;13(17): 5150-5 (Pubitemid 47502083
77. Katayama R, Shaw AT, Khan TM, et al. Mechanisms of acquired crizotinib resistance in ALK-rearranged lung cancers. Sci Transl Med 2012;4(120):120ra117
78. Doebele RC, Pilling AB, Aisner DL, et al. Mechanisms of resistance to crizotinib in patients with ALK gene rearranged non-small cell lung cancer. Clin Cancer Res 2012;18(5):1472-82
79. Choi YL, Soda M, Yamashita Y, et al. EML4-ALK mutations in lung cancer that confer resistance to ALK inhibitors. N EnglJ Med 2010;363(18):1734-9
80. Katayama R, Khan TM, Benes C, et al. Therapeutic strategies to overcome crizotinib resistance in non-small cell lung cancers harboring the fusion oncogene EML4-ALK. Proc Natl Acad Sci USA 2011;108(18): 7535-40
81. Camidge DR, Bazhenova L, Salgia R, et al. First-in-human dose-finding study of the ALK/EGFR inhibitor AP26113 in patients with advanced malignancies: Updated results. J Clin Oncol 2013;31(Suppl): abstract 8031
82. Chen J, Jiang C, Wang S. LDK378: a promising Anaplastic Lymphoma Kinase (ALK) inhibitor. J Med Chem 2013;56(14): 5673-4
83. Leon SA, Shapiro B, Sklaroff DM, Yaros MJ. Free DNA in the serum of cancer patients and the effect of therapy. Cancer Res 1977;37(3):646-50 (Pubitemid 8051621
84. Kopreski MS, Benko FA, Borys DJ, et al. Somatic mutation screening: identification of individuals harboring K-ras mutations with the use of plasma DNA. J Natl Cancer Inst 2000;92(11):918-23 (Pubitemid 30429192
85. Mouliere F, Robert B, Arnau Peyrotte E, et al. High fragmentation characterizes tumour-derived circulating DNA. PLoS One 2011;6(9):e23418
86. Anker P, Mulcahy H, Chen XQ, Stroun M. Detection of circulating tumour DNA in the blood (plasma/serum) of cancer patients. Cancer Metastasis Rev 1999;18(1): 65-73 (Pubitemid 29411092
87. Henderson MC, Azorsa DO. The genomic and proteomic content of cancer cell-derived exosomes. Front Oncol 2012;2:38
88. Jahr S, Hentze H, Englisch S, et al. DNA fragments in the blood plasma of cancer patients: quantitations and evidence for their origin from apoptotic and necrotic cells. Cancer Res 2001;61(4): 1659-65 (Pubitemid 34292602
89. Stroun M, Maurice P, Vasioukhin V, et al. The origin and mechanism of circulating DNA. Ann N Y Acad Sci 2000;906:161-8 (Pubitemid 30255476
90. Murtaza M, Dawson SJ, Tsui DW, et al. Non-invasive analysis of acquired resistance to cancer therapy by sequencing of plasma DNA. Nature 2013;497(7447):108-12
91. Punnoose EA, Atwal S, Liu W, et al. Evaluation of circulating tumor cells and circulating tumor DNA in non-small cell lung cancer: association with clinical endpoints in a phase II clinical trial of pertuzumab and erlotinib. Clin Cancer Res 2012;18(8):2391-401
92. Thierry AR, Mouliere F, Gongora C, et al. Origin and quantification of circulating DNA in mice with human colorectal cancer xenografts. Nucleic Acids Res 2010;38(18): 6159-75
93. Umetani N, Hiramatsu S, Hoon DS. Higher amount of free circulating DNA in serum than in plasma is not mainly caused by contaminated extraneous DNA during separation. Ann N Y Acad Sci 2006;1075: 299-307 (Pubitemid 44532797
94. Yung TK, Chan KC, Mok TS, et al. Single-molecule detection of epidermal growth factor receptor mutations in plasma by microfluidics digital PCR in non-small cell lung cancer patients. Clin Cancer Res 2009;15(6):2076-84
95. Forshew T, Murtaza M, Parkinson C, et al. Noninvasive identification and monitoring of cancer mutations by targeted deep sequencing of plasma DNA. Sci Transl Med 2012;4(136):136ra168
96. Wilkening S, Hemminki K, Thirumaran RK, et al. Determination of allele frequency in pooled DNA: comparison of three PCR-based methods. Biotechniques 2005;39(6):853-8
97. Hindson BJ, Ness KD, Masquelier DA, et al. High-throughput droplet digital PCR system for absolute quantitation of DNA copy number. Anal Chem 2011; 83(22):8604-10
98. Li J, Wang L, Mamon H, et al. Replacing PCR with COLD-PCR enriches variant DNA sequences and redefines the sensitivity of genetic testing. Nat Med 2008;14(5): 579-84 (Pubitemid 351655208
99. Brevet M, Johnson ML, Azzoli CG, Ladanyi M. Detection of EGFR mutations in plasma DNA from lung cancer patients by mass spectrometry genotyping is predictive of tumor EGFR status and response to EGFR inhibitors. Lung Cancer 2011;73(1):96-102
100. Diehl F, Li M, Dressman D, et al. Detection and quantification of mutations in the plasma of patients with colorectal tumors. Proc Natl Acad Sci USA 2005; 102(45):16368-73 (Pubitemid 41688920
101. Kimura H, Suminoe M, Kasahara K, et al. Evaluation of epidermal growth factor receptor mutation status in serum DNA as a predictor of response to gefitinib (IRESSA). Br J Cancer 2007;97(6):778-84 (Pubitemid 47396294
102. Taniguchi K, Uchida J, Nishino K, et al. Quantitative detection of EGFR mutations in circulating tumor DNA derived from lung adenocarcinomas. Clin Cancer Res 2011;17(24):7808-15
103. Uchida J, Niki T, Okuyama T, et al. Analysis of circulating tumor EGFR-DNA in plasma during EGFR-TKI therapy of EGFR mutation-positive lung cancer patients. Ann Oncol 2013; 24(Suppl 9):abstract O3-070
104. Sorensen B, Wu L, Wen W, et al. Monitoring of EGFR TKI sensitizing and resistance mutations in plasma DNA of advanced adenocarcinoma of NSCLC during erlotinib treatment. J Thorac Oncol 2013;8(Suppl 2):abstract MO21.07
105. Aoe K, Sueoka-Aragane N, Katakami N, et al. Monitoring EGFR T790M with plasma DNA in lung cancer patients treated with EGFR tyrosine kinase inhibitor in prospective observational study. J Thorac Oncol 2013;8(Suppl 2):abstract MO06.02
106. Wakelee HA, Karlovich CA, Wen W, et al. Serial monitoring of plasma EGFR T790M levels and evaluation of EGFR mutational status in matched tissue and plasma from NSCLC patients treated with CO-1686. J Thorac Oncol 2013;8(Suppl 2):abstract MO21.10
107. Leary RJ, Sausen M, Kinde I, et al. Detection of chromosomal alterations in the circulation of cancer patients with whole-genome sequencing. Sci Transl Med 2012;4(162):162ra154
108. Pailler E, Adam J, Barthelemy A, et al. Detection of circulating tumor cells harboring a unique ALK rearrangement in ALK-positive non-small-cell lung cancer. J Clin Oncol 2013;31(18):2273-81
109. Katakami N, Atagi S, Goto K, et al. LUX-Lung 4: a phase II trial of afatinib in patients with advanced non-small-cell lung cancer who progressed during prior treatment with erlotinib, gefitinib, or both. J Clin Oncol 2013;31(27):3335-41
110. Maheswaran S, Sequist LV, Nagrath S, et al. Detection of mutations in EGFR in circulating lung-cancer cells. N Engl J Med 2008;359(4):366-77
111. Kuang Y, Rogers A, Yeap BY, et al. Noninvasive detection of EGFR T790M in gefitinib or erlotinib resistant non-small cell lung cancer. Clin Cancer Res 2009;15(8): 2630-6
112. Maemondo M, Nishio M, Yamamoto N, et al. Variability of epidermal growth factor receptor (EGFR) mutations in serum during erlotinib therapy and its clinical implications: exploratory analysis of a phase II study of erlotinib in patients with advanced non-small-cell lung cancer (NSCLC) harboring. J Thorac Oncol 2013; 8(Suppl 2):Abstract MO21.03
113. Chen R, Bai H, Wang S, et al. Dynamic, quantitative, and non-invasive analysis of T790M mutation in matched plasma DNA from pre-and post-EGFR-TKI treatment for advanced non-small cell lung cancer. J Thorac Oncol 2013; 8(Suppl 2):Abstract MO21.09
114. Nakamura T, Sueoka-Aragane N, Iwanaga K, et al. Application of a highly sensitive detection system for epidermal growth factor receptor mutations in plasma DNA. J Thorac Oncol 2012;7(9):1369-81