Current and future molecular diagnostics in non-small-cell lung cancer

References

• World Cancer Research Fund International. Worldwide data. 2015. Available from: www.wcrf.org/int/cancer-facts-figures/wordwide-data [Last accessed 15 March 2015]
   Google Scholar
• Top ten cancers in 2012. Hong Kong Cancer Registry 2012. Available from: www3.ha.org.hk/cancereg/statistics.html [Last accessed 15 March 2015]
   Google Scholar
• Plass D, Chau PY, Thach TQ, et al. Quantifying the burden of disease due to premature mortality in Hong Kong using standard expected years of life lost. BMC Public Health 2013;13:863
   PubMed Web of Science ®Google Scholar
• Kim C, Chapman RS, Hu W, et al. Smoky coal, tobacco smoking, and lung cancer risk in Xuanwei, China. Lung Cancer 2014;84:31-5
   Google Scholar
• Yu IT, Chiu YL, Au JS, et al. Dose-response relationship between cooking fumes exposures and lung cancer among Chinese nonsmoking women. Cancer Res 2006;66:4961-7
   PubMed Web of Science ®Google Scholar
• Zhang ZL, Sun J, Dong JY, et al. Residential radon and lung cancer risk: an updated meta-analysis of case-control studies. Asian Pac J Cancer Prev 2012;13:2459-65
   PubMedGoogle Scholar
• Yang M. A current global view of environmental and occupational cancers. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev 2011;29:223-49
   PubMed Web of Science ®Google Scholar
• Sion-Vardy N, Lasarov I, Delgado B, et al. Measles virus: evidence for association with lung cancer. Exp Lung Res 2009;35:701-12
   PubMed Web of Science ®Google Scholar
• Gaughan EM, Cryer SK, Yeap BY, et al. Family history of lung cancer in never smokers with non-small-cell lung cancer and its association with tumors harboring EGFR mutations. Lung Cancer 2013;79:193-7
   PubMed Web of Science ®Google Scholar
• Chan OS, Yeung RM and Lee AW. Maintenance therapy in advanced non-small cell lung cancer: a prime-time for change? Chin Med J (Engl) 2013;126:2390-8
   Google Scholar
• Howlader N, Noone AM, Krapcho M, et al. SEER Cancer Statistics Review, 1975-2010. National Cancer Institute. Bethesda, MD. Available from: http://seer.cancer.gov/csr/1975_2010/ [Last accessed 15 March 2014]
   Google Scholar
• Field JK, Oudkerk M, Pedersen JH, et al. Prospects for population screening and diagnosis of lung cancer. Lancet 2013;382:732-41
   PubMed Web of Science ®Google Scholar
• Coate LE, John T, Tsao MS, et al. Molecular predictive and prognostic markers in non-small-cell lung cancer. Lancet Oncol 2009;10:1001-10
   PubMed Web of Science ®Google Scholar
• Rosell R, Bivona TG, Karachaliou N. Genetics and biomarkers in personalisation of lung cancer treatment. Lancet 2013;382:720-31
   PubMed Web of Science ®Google Scholar
• Liloglou T, Bediaga NG, Brown BR, et al. Epigenetic biomarkers in lung cancer. Cancer Lett 2014;342:200-12
   PubMed Web of Science ®Google Scholar
• Travis WD, Brambilla E, Noguchi M, et al. International association for the study of lung cancer/american thoracic society/european respiratory society international multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol 2011;6:244-85
   PubMed Web of Science ®Google Scholar
• Devesa SS, Bray F, Vizcaino AP, et al. International lung cancer trends by histologic type: male:female differences diminishing and adenocarcinoma rates rising. Int J Cancer 2005;117:294-9
   PubMed Web of Science ®Google Scholar
• Riely GJ, Politi KA, Miller VA, et al. Update on epidermal growth factor receptor mutations in non-small cell lung cancer. Clin Cancer Res 2006;12:7232-41
   PubMed Web of Science ®Google Scholar
• Cooper WA, Lam DC, O’Toole SA, et al. Molecular biology of lung cancer. J Thorac Dis 2013;5(Suppl 5):S479-90
   PubMedGoogle Scholar
• New and emerging health technologies for lung cancer. University of Birmingham. National Institute for Health Research Horizon Scanning Centre, 2013, Table 7 p54. Available from: http://www.hsc.nihr.ac.uk/files/downloads/2147/2464.0f83be64.Non confidentialversionLungCancerReport.pdf [Last accessed March 2015]
   Google Scholar
• Ellison G, Zhu G, Moulis A, et al. EGFR mutation testing in lung cancer: a review of available methods and their use for analysis of tumour tissue and cytology samples. J Clin Pathol 2013;66:79-89
   PubMed Web of Science ®Google Scholar
• Lindeman NI, Cagle PT, Beasley MB, et al. Molecular testing guideline for selection of lung cancer patients for EGFR and ALK tyrosine kinase inhibitors: guideline from the college of American pathologists, international association for the study of lung cancer, and association for molecular pathology. Arch Pathol Lab Med 2013;137:828-60
   PubMed Web of Science ®Google Scholar
• Kim H, Shim HS, Kim L, et al. Guideline recommendations for testing of ALK gene rearrangement in lung cancer: a proposal of the Korean Cardiopulmonary Pathology Study Group. Korean J Pathol 2014;48:1-9
   Google Scholar
• Yam I, Lam DC, Chan K, et al. EGFR array: uses in the detection of plasma EGFR mutations in non-small cell lung cancer patients. J Thorac Oncol 2012;7:1131-40
   PubMed Web of Science ®Google Scholar
• Dahabreh IJ, Linardou H, Siannis F, et al. Somatic EGFR mutation and gene copy gain as predictive biomarkers for response to tyrosine kinase inhibitors in non-small cell lung cancer. Clin Cancer Res 2010;16:291-303
   PubMed Web of Science ®Google Scholar
• Da Cunha Santos G, Shepherd FA, Tsao MS. EGFR mutations and lung cancer. Annu Rev Pathol 2011;6:49-69
   PubMed Web of Science ®Google Scholar
• Rekhtman N, Paik PK, Arcila ME, et al. Clarifying the spectrum of driver oncogene mutations in biomarker-verified squamous carcinoma of lung: lack of EGFR/KRAS and presence of PIK3CA/AKT1 mutations. Clin Cancer Res 2012;18:1167-76
   PubMed Web of Science ®Google Scholar
• Lynch TJ, Bell DW, Sordella R, et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 2004;350:2129-39
   PubMed Web of Science ®Google Scholar
• Mok TS, Wu YL, Thongprasert S, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 2009;361:947-57
   PubMed Web of Science ®Google Scholar
• Lee VW, Schwander B, Lee VH. Effectiveness and cost-effectiveness of erlotinib versus gefitinib in first-line treatment of epidermal growth factor receptor-activating mutation-positive non-small-cell lung cancer patients in Hong Kong. Hong Kong Med J 2014;20:178-86
   PubMed Web of Science ®Google Scholar
• Oxnard GR, Arcila ME, Chmielecki J, et al. New strategies in overcoming acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in lung cancer. Clin Cancer Res 2011;17:5530-7
   PubMed Web of Science ®Google Scholar
• 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;15:2076-84
   PubMed Web of Science ®Google Scholar
• Zhao J, Zhao J, Huang J, et al. A novel method for detection of mutation in epidermal growth factor receptor. Lung Cancer 2011;74:226-32
   Google Scholar
• QIAGEN. Product Page: Therascreen EGFR Pyro Kit. Available from: www.qiagen.com/Products/Catalog/Assay-Technologies/Complete-Assay-Kits/Personalized-Healthcare/therascreen-EGFR-Pyro-Kit#orderinginformation [Last accessed 15 March 2014]
   Google Scholar
• Roche molecular diagnostic. Product: Cobas EGFR mutation Test. Available from: http://molecular.roche.com/assays/Pages/cobasEGFRMutationTest.aspx [Last accessed 15 March 2014]
   Google Scholar
• Wong AT, To RM, Wong CL, et al. Evaluation of 2 real-time PCR assays for in vitro diagnostic use in the rapid and multiplex detection of EGFR gene mutations in NSCLC. Diagn Mol Pathol 2013;22:138-43
   Google Scholar
• Lee VH, Tin VP, Choy TS, et al. Association of exon 19 and 21 EGFR mutation patterns with treatment outcome after first-line tyrosine kinase inhibitor in metastatic non-small-cell lung cancer. J Thorac Oncol 2013;8:1148-55
   Google Scholar
• Shaw AT, Yeap BY, Mino-Kenudson M, et al. Clinical features and outcome of patients with non-small-cell lung cancer who harbor EML4-ALK. J Clin Oncol 2009;27:4247-53
   PubMed Web of Science ®Google Scholar
• Pao W, Girard N. New driver mutations in non-small-cell lung cancer. Lancet Oncol 2011;12:175-80
   PubMed Web of Science ®Google Scholar
• Gainor JF, Varghese AM, Ou SH, et al. ALK rearrangements are mutually exclusive with mutations in EGFR or KRAS: an analysis of 1,683 patients with non-small cell lung cancer. Clin Cancer Res 2013;19:4273-81
   PubMed Web of Science ®Google Scholar
• Malik SM, Maher VE, Bijwaard KE, et al. U.S. Food and Drug Administration Approval: Crizotinib for Treatment of Advanced or Metastatic Non-small Cell Lung Cancer that Is Anaplastic Lymphoma Kinase Positive. Clin Cancer Res 2014;20:2029-34
   PubMed Web of Science ®Google Scholar
• Katayama R, Shaw AT, Khan TM, et al. Mechanisms of acquired crizotinib resistance in ALK rearranged lung cancers. Sci Transl Med 2012;4(120):120ra17
   PubMed Web of Science ®Google Scholar
• 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;18:1472-82
   PubMed Web of Science ®Google Scholar
• Tuononen K, Sarhadi VK, Wirtanen A, et al. Targeted resequencing reveals ALK fusions in non-small cell lung carcinomas detected by FISH, immunohistochemistry, and real-time RT-PCR: a comparison of four methods. Biomed Res Int 2013;2013:757490
   PubMed Web of Science ®Google Scholar
• To KF, Tong JH, Yeung KS, et al. Detection of ALK rearrangement by immunohistochemistry in lung adenocarcinoma and the identification of a novel EML4-ALK variant. J Thorac Oncol 2013;8:883-91
   Google Scholar
• Go H, Jeon YK, Park HJ, et al. High MET gene copy number leads to shorter survival in patients with non-small cell lung cancer. J Thorac Oncol 2010;3:305-13
   Google Scholar
• Cappuzzo F, Marchetti A, Skokan M, et al. Increased MET gene copy number negatively affects survival of surgically resected non-small-cell lung cancer patients. J Clin Oncol 2009;27:1667-74
   PubMed Web of Science ®Google Scholar
• 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. J Clin Oncol 2011;29:3307-15
   PubMed Web of Science ®Google Scholar
• 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. J Clin Oncol 2013;31:4105-14
   PubMed Web of Science ®Google Scholar
• Davies KD, Doebele RC. Molecular pathways: ROS1 fusion in cancer. Clin Cancer Res 2013;15:4040-5
   Google Scholar
• Anjum R, Zhang S, Squillace R, et al. The Dual ALK/EGFR Inhibitor AP26113 also potently inhibits activated and gatekeeper mutant forms of ROS1. Eur J Cancer 2012;48:50
   Google Scholar
• Shaw AT, Camidge DR, Engelman JA, et al. Clinical activity of crizotinib in advanced non-small cell lung cancer (NSCLC) harboring ROS1 gene rearrangement. J Clin Oncol 2012;30(Suppl):abstract 7508
   Google Scholar
• Park BS, Al-Sanea MM, Abdelazem AZ, et al. Structure-based optimization and biological evaluation of trisubstituted pyrazole as a core structure of potent ROS1 kinase inhibitors. Bioorg Med Chem 2014;22:3871-8
   Google Scholar
• A Phase 1/2 Study of the Oral ALK/EGFR Inhibitor AP26113. Available from: www.clinicaltrials.gov/ct2/show/record/NCT01449461?term=01449461&rank=1 [Last accessed 15 June 2014]
   Google Scholar
• Mescam-Mancini L, Lantuejoul S, Sibilot DM, et al. On the relevance of a testing algorithm for the detection of ROS1-rearranged lung adenocarcinomas. Lung Cancer 2014;83:168-73
   PubMed Web of Science ®Google Scholar
• Massarelli E, Varella-Garcia M, Tang X, et al. KRAS mutation is an important predictor of resistance to therapy with epidermal growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancer. Clin Cancer Res 2007;13:2890-6
   PubMed Web of Science ®Google Scholar
• Stella GM, Scabini R, Inghilleri S, et al. EGFR and KRAS mutational profiling in fresh non-small cell lung cancer (NSCLC) cells. J Cancer Res Clin Oncol 2013;139:1327-35
   PubMed Web of Science ®Google Scholar
• Jänne PA, Shaw AT, Pereira JR, et al. Selumetinib plus docetaxel for KRAS-mutant advanced non-small-cell lung cancer: a randomised, multicentre, placebo-controlled, phase 2 study. Lancet Oncol 2013;14(1):38-47
   PubMed Web of Science ®Google Scholar
• QIAGEN. Product Page: Therascreen KRAS Pyro Kit. Available from: www.qiagen.com/products/catalog/assay-technologies/complete-assay-kits/personalized-healthcare/therascreen-kras-pyro-kit [Last accessed 15 March 2014]
   Google Scholar
• Roche molecular diagnostic. Product: TheraScreen KRAS mutation Kit. Available from: www.oem-info.com/roche/handbooks/data/DU001g_KRAS_TheraScreen_ENGLISH.pdf [Last accessed 15 March 2014]
   Google Scholar
• Oasia Diagnostics. Genomics Products. Available from: http://4saliva.com/genomics/k-ras/ [Last accessed 15 March 2014]
   Google Scholar
• Brustugun OT, Khattak AM, Trømborg AK, et al. BRAF-mutations in non-small cell lung cancer. Lung Cancer 2014;84:36-8
   PubMed Web of Science ®Google Scholar
• Oikonomou E, Koustas E, Goulielmaki M, et al. BRAF vs RAS oncogenes: are mutations of the same pathway equal? Differential signalling and therapeutic implications. Oncotarget 2014;5:11752-77
   PubMed Web of Science ®Google Scholar
• Mar N, Vredenburgh JJ, Wasser JS. Targeting HER2 in the treatment of non-small cell lung cancer. Lung Cancer 2015;87:220-5
   PubMed Web of Science ®Google Scholar
• Mazières J, Peters S, Lepage B, et al. Lung cancer that harbors an HER2 mutation: epidemiologic characteristics and therapeutic perspectives. J Clin Oncol 2013;31:1997-2003
   PubMed Web of Science ®Google Scholar
• Gainor JF, Shaw AT. Novel targets in non-small cell lung cancer: ROS1 and RET fusions. Oncologist 2013;18:865-75
   PubMed Web of Science ®Google Scholar
• Wang R, Hu H, Pan Y, et al. RET fusions define a unique molecular and clinicopathologic subtype of non-small-cell lung cancer. J Clin Oncol 2012;30:4352-9
   PubMed Web of Science ®Google Scholar
• Drilon A, Wang L, Hasanovic A, et al. Response to Cabozantinib in patients with RET fusion-positive lung adenocarcinomas. Cancer Discov 2013;3:630-5
   PubMed Web of Science ®Google Scholar
• Greulich H, Pollock PM. Targeting mutant fibroblast growth factor receptors in cancer. Trends Mol Med 2011;17:283-92
   PubMed Web of Science ®Google Scholar
• Sasaki H, Shitara M, Yokota K, et al. Increased FGFR1 copy number in lung squamous cell carcinomas. Mol Med Rep 2012;5:725-8
   Google Scholar
• Kohler LH, Mireskandari M, Knösel T, et al. FGFR1 expression and gene copy numbers in human lung cancer. Virchows Arch 2012;461:49-57
   PubMed Web of Science ®Google Scholar
• Dutt A, Ramos AH, Hammerman PS, et al. Inhibitor-sensitive FGFR1 amplification in human non-small cell lung cancer. PLoS One 2011;6:e20351
   PubMed Web of Science ®Google Scholar
• Kim HR, Kim DJ, Kang DR, et al. Fibroblast growth factor receptor 1 gene amplification is associated with poor survival and cigarette smoking dosage in patients with resected squamous cell lung cancer. J Clin Oncol 2013;31:731-7
   PubMed Web of Science ®Google Scholar
• Seo AN, Jin Y, Lee HJ, et al. FGFR1 amplification is associated with poor prognosis and smoking in non-small-cell lung cancer. Virchows Arch 2014;465:547-58
   PubMed Web of Science ®Google Scholar
• Cihoric N, Savic S, Schneider S, et al. Prognostic role of FGFR1 amplification in early-stage non-small cell lung cancer. Br J Cancer 2014;110:2914-22
   PubMed Web of Science ®Google Scholar
• Ren M, Hong M, Liu G, et al. Novel FGFR inhibitor ponatinib suppresses the growth of non-small cell lung cancer cells overexpressing FGFR1. Oncol Rep 2013;29:2181-90
   PubMed Web of Science ®Google Scholar
• Borza CM, Pozzi A. Discoidin domain receptors in disease. Matrix Biol 2014;34:185-92
   PubMed Web of Science ®Google Scholar
• 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;1:78-89
   PubMed Web of Science ®Google Scholar
• Miao L, Wang Y, Zhu S, et al. Identification of novel driver mutations of the discoidin domain receptor 2 (DDR2) gene in squamous cell lung cancer of Chinese patients. BMC Cancer 2014;14:369
   PubMed Web of Science ®Google Scholar
• Abdulkareem IH, Blair M. Phosphatase and tensin homologue deleted on chromosome 10. Niger Med J 2013;54:79-86
   Google Scholar
• Yamamoto C, Basaki Y, Kawahara A, et al. Loss of PTEN expression by blocking nuclear translocation of EGR1 in gefitinib-resistant lung cancer cells harboring epidermal growth factor receptor-activating mutations. Cancer Res 2010;70:8715-25
   Google Scholar
• Takeda H, Takigawa N, Ohashi K, et al. Vandetanib is effective in EGFR-mutant lung cancer cells with PTEN deficiency. Exp Cell Res 2013;319:417-23
   Google Scholar
• Samuels Y, Waldman T. Oncogenic mutations of PIK3CA in human cancers. Curr Top Microbiol Immunol 2010;347:21-41
   PubMed Web of Science ®Google Scholar
• Akinleye A, Avvaru P, Furqan M, et al. Phosphatidylinositol 3-kinase (PI3K) inhibitors as cancer therapeutics. J Hematol Oncol 2013;6:88
   PubMed Web of Science ®Google Scholar
• Niederst MJ, Engelman JA. Bypass mechanisms of resistance to receptor tyrosine kinase inhibition in lung cancer. Sci Signal 2013;6:re6
   PubMed Web of Science ®Google Scholar
• Brown KK, Toker A. The phosphoinositide 3-kinase pathway and therapy resistance in cancer. F1000Prime Rep 2015;7:13
   PubMedGoogle Scholar
• Fruman DA, Rommel C. PI3K and cancer: lessons, challenges and opportunities. Nat Rev Drug Discov 2014;13:140-56
   PubMed Web of Science ®Google Scholar
• Lee H, Kim SJ, Jung KH. A novel imidazopyridine PI3K inhibitor with anticancer activity in non-small cell lung cancer cells. Oncol Rep 2013;30:863-9
   Google Scholar
• Wong MK, Ho JC, Loong F, et al. Endobronchial ultrasound-guided transbronchial needle aspiration in lung cancer: the first experience in Hong Kong. Hong Kong Med J 2013;19:20-6
   Google Scholar
• Schmid-Bindert G, Wang Y, Jiang H, et al. EBUS-TBNA provides highest RNA yield for multiple biomarker testing from routinely obtained small biopsies in non-small cell lung cancer patients - a comparative study of three different minimal invasive sampling methods. PLoS One 2013;8:e77948
   PubMedGoogle Scholar
• Chan KC, Jiang P, Zheng YW, et al. Cancer genome scanning in plasma: detection of tumor-associated copy number aberrations, single-nucleotide variants, and tumoral heterogeneity by massively parallel sequencing. Clin Chem 2013;59:211-24
   PubMed Web of Science ®Google Scholar
• Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 2004;116:281-97
   PubMed Web of Science ®Google Scholar
• Shen J, Jiang F. Applications of MicroRNAs in the Diagnosis and prognosis of Lung Cancer. Expert Opin Med Diagn 2012;6:197-207
   PubMedGoogle Scholar
• Qi J, Mu D. MicroRNAs and lung cancers: from pathogenesis to clinical implications. Front Med 2012;6:134-55
   Google Scholar
• miRBase. Available from: www.mirbase.org [Last accessed 15 March 2014]
   Google Scholar
• Costa PM, Pedroso de Lima MC. MicroRNAs as molecular targets for cancer therapy: on the modulation of microRNA expression. Pharmaceuticals (Basel) 2013;6:1195-220
   Google Scholar
• Hubers AJ, Prinsen CF, Sozzi G, et al. Molecular sputum analysis for the diagnosis of lung cancer. Br J Cancer 2013;109:530-7
   PubMed Web of Science ®Google Scholar
• Wong SC, Lo SF, Cheung MT, et al. Quantification of plasma beta-catenin mRNA in colorectal cancer and adenoma patients. Clin Cancer Res 2004;10:1613-17
   PubMed Web of Science ®Google Scholar
• Plönes T, Elze M, Kayser G, et al. mRNA and miRNA analyses in cytologically positive endobronchial ultrasound-guided transbronchial needle aspiration: Implications for molecular staging in lung cancer patients. Cancer Cytopathol 2014;122:292-8
   PubMed Web of Science ®Google Scholar
• Pritchard CC, Kroh E, Wood B, et al. Blood cell origin of circulating microRNAs: a cautionary note for cancer biomarker studies. Cancer Prev Res (Phila) 2012;5:492-7
   PubMed Web of Science ®Google Scholar
• Hennessey PT, Sanford T, Choudhary A, et al. Serum microRNA biomarkers for detection of non-small cell lung cancer. PLoS One 2012;7:e32307
   PubMed Web of Science ®Google Scholar
• Liu XG, Zhu WY, Huang YY, et al. High expression of serum miR-21 and tumor miR-200c associated with poor prognosis in patients with lung cancer. Med Oncol 2012;29:618-26
   PubMed Web of Science ®Google Scholar
• Bianchi L, Nicassio F, Marzi M, et al. A serum circulating miRNA diagnostic test to identify asymptomatic high-risk individuals with early stage lung cancer. EMBO Mol Med 2011;3:495-503
   PubMed Web of Science ®Google Scholar
• Whale AS, Huggett JF, Cowen S, et al. Comparison of microfluidic digital PCR and conventional quantitative PCR for measuring copy number variation. Nucleic Acids Res 2012;40:e82
   PubMed Web of Science ®Google Scholar
• Ma J, Li N, Guarnera M, et al. Quantification of plasma miRNAs by digital PCR for cancer diagnosis. Biomark Insights 2013;8:127-36
   PubMedGoogle Scholar
• Daskalos A, Nikolaidis G, Xinarianos G, et al. Hypomethylation of retrotransposable elements correlates with genomic instability in non-small cell lung cancer. Int J Cancer 2009;124:81-7
   PubMed Web of Science ®Google Scholar
• Kerr KM, Galler JS, Hagen JA, et al. The role of DNA methylation in the development and progression of lung adenocarcinoma. Dis Markers 2007;23:5-30
   PubMed Web of Science ®Google Scholar
• Balgkouranidou I, Liloglou T, Lianidou ES. Lung cancer epigenetics: emerging biomarkers. Biomark Med 2013;7:49-58
   PubMed Web of Science ®Google Scholar
• Dietrich D, Kneip C, Raji O, et al. Performance evaluation of the DNA methylation biomarker SHOX2 for the aid in diagnosis of lung cancer based on the analysis of bronchial aspirates. Int J Oncol 2012;40:825-32
   PubMed Web of Science ®Google Scholar
• Kneip C, Schmidt B, Seegebarth A, et al. SHOX2 DNA methylation is a biomarker for the diagnosis of lung cancer in plasma. J Thorac Oncol 2011;6:1632-8
   PubMed Web of Science ®Google Scholar
• Chan KC, Jiang P, Chan CW, et al. Noninvasive detection of cancer-associated genome-wide hypomethylation and copy number aberrations by plasma DNA bisulfite sequencing. Proc Natl Acad Sci USA 2013;110:18761-8
   PubMed Web of Science ®Google Scholar
• Lee Y, Kim HY, Lee SH, et al. Clinical significance of heterogeneity in response to retreatment with epidermal growth factor receptor tyrosine kinase inhibitors in patients with lung cancer acquiring secondary resistance to the drug. Clin Lung Cancer 2014;15:145-51
   Google Scholar
• Bai H, Wang Z, Wang Y, et al. Detection and clinical significance of intratumoral EGFR mutational heterogeneity in Chinese patients with advanced non-small cell lung cancer. PLoS One 2013;8:e54170
   PubMed Web of Science ®Google Scholar
• Jiang SX, Yamashita K, Yamamoto M, et al. EGFR genetic heterogeneity of nonsmall cell lung cancers contributing to acquired gefitinib resistance. Int J Cancer 2008;123:2480-6
   PubMed Web of Science ®Google Scholar
• Cagle PT, Allen TC, Olsen RJ. Lung cancer biomarkers present status and future developments. Arch Pathol Lab Med 2013;137:1191-8
   Google Scholar
• Cai G, Wong R, Chhieng D, et al. Identification of EGFR mutation, KRAS mutation, and ALK gene rearrangement in cytological specimens of primary and metastatic lung adenocarcinoma. Cancer Cytopathol 2013;121:500-7
   Google Scholar
• Thunnissena T, Kerrb KM, Herthc FJ, et al. The challenge of NSCLC diagnosis and predictive analysis on small samples. Practical approach of a working group. Lung Cancer 2012;6:1-18
   Google Scholar
• Querings S, Altmüller J, Ansén S, et al. Benchmarking of mutation diagnostics in clinical lung cancer specimens. PLoS One 2011;6:e19601
   Web of Science ®Google Scholar
• Jung CY. Biopsy and mutation detection strategies in non-small cell lung cancer. Tuberc Respir Dis 2013;75:181-7
   Google Scholar
• Mino-Kenudson M, Chirieac LR, Law K, et al. A novel, highly sensitive antibody allows for the routine detection of ALK-rearranged lung adenocarcinomas by standard immunohistochemistry. Clin Cancer Res 2010;16:1561-71
   PubMed Web of Science ®Google Scholar
• Sholl LM, Weremowicz S, Gray SW, et al. Combined use of ALK immunohistochemistry and FISH for optimal detection of ALK-rearranged lung adenocarcinomas. J Thorac Oncol 2013;8:322-8
   PubMed Web of Science ®Google Scholar
• Rogers TM, Russell PA, Wright G, et al. Comparison of methods in the detection of ALK and ROS1 rearrangements in lung cancer. J Thorac Oncol 2015;10:611-18
   PubMed Web of Science ®Google Scholar
• Von Laffert M, Warth A, Penzel R, et al. Multicenter immunohistochemical ALK-testing of non-small-cell lung cancer shows high concordance after harmonization of techniques and interpretation criteria. J Thorac Oncol 2014;9:1685-92
   PubMed Web of Science ®Google Scholar
• Uguen A, Talagas M, Andrieu-Key S, et al. ALK FISH rearranged and amplified tumor with negative immunohistochemistry: a rare and challenging case concerning ALK status screening in lung cancer. Ann Oncol 2015. [Epub ahead of print]
   Google Scholar
• Llie Ml, Bence C, Hofman V, et al. Discrepancies between FISH and immunohistochemistry for assessment of the ALK status are associated with ALK ‘borderline’-positive rearrangements or a high copy number: a potential major issue for anti-ALK therapeutic strategies. Ann Oncol 2015;26:238-44
   Google Scholar
• Allo G, Bandarchi B, Yanagawa N, et al. Epidermal growth factor receptor mutation-specific immunohistochemical antibodies in lung adenocarcinoma. Histopathology 2014;64:826-39
   Google Scholar
• Wen YH, Brogi E, Hasanovic A, et al. Immunohistochemical staining with EGFR mutation-specific antibodies: high specificity as a diagnostic marker for lung adenocarcinoma. Mod Pathol 2013;26:1197-203
   Google Scholar
• Warth A, Muley T, Dienemann H, et al. ROS1 expression and translocations in non-small-cell lung cancer: clinicopathological analysis of 1478 cases. Histopathology 2014;65:187-94
   PubMed Web of Science ®Google Scholar
• Yoshida A, Tsuta K, Wakai S, et al. Immunohistochemical detection of ROS1 is useful for identifying ROS1 rearrangements in lung cancers. Mod Pathol 2014;27:711-20
   PubMed Web of Science ®Google Scholar
• Jiang G, Fan C, Zhang X, et al. Ascertaining an appropriate diagnostic algorithm using EGFR mutation-specific antibodies to detect EGFR status in non-small-cell lung cancer. PLoS One 2013;8:e59183
   Google Scholar
• Bentley DR, Balasubramanian S, Swerdlow HP, et al. Accurate whole human genome sequencing using reversible terminator chemistry. Nature 2008;456:53-9
   PubMed Web of Science ®Google Scholar
• Thomas A, Rajan A, Lopez-Chavez A, et al. From targets to targeted therapies and molecular profiling in non-small cell lung carcinoma. Ann Oncol 2013;24:577-85
   PubMed Web of Science ®Google Scholar
• Dacic S, Nikiforova MN. Present and future molecular testing of lung carcinoma. Adv Anat Pathol 2014;21:94-9
   PubMed Web of Science ®Google Scholar
• Summerer D. Enabling technologies of genomic-scale sequence enrichment for targeted high-throughput sequencing. Genomics 2009;94:363-8
   PubMed Web of Science ®Google Scholar
• Shames DS, Wistuba II. The evolving genomic classification of lung cancer. J Pathol 2014;232:121-33
   PubMed Web of Science ®Google Scholar
• Cancer Genome Atlas Research Network. Weinstein JN, Collisson EA, et al. The cancer genome atlas pan-cancer analysis project. Nat Genet 2013;45:1113-20
   PubMed Web of Science ®Google Scholar
• Imielinski M, Berger AH, Hammerman PS, et al. Mapping the hallmarks of lung adenocarcinoma with massively parallel sequencing. Cell 2012;150:1107-20
   PubMed Web of Science ®Google Scholar
• Cancer Genome Atlas Research Network. Comprehensive genomic characterization of squamous cell lung cancers. Nature 2012;489:519-25
   PubMed Web of Science ®Google Scholar
• Cancer Genome Atlas Research Network. Comprehensive molecular profiling of lung adenocarcinoma. Nature 2014;511:543-50
   PubMed Web of Science ®Google Scholar
• Carney DN, Gazdar AF, Bunn PAJr, et al. Demonstration of the stem cell nature of clonogenic tumor cells from lung cancer patients. Stem Cells 1982;1:149-64
   PubMedGoogle Scholar
• Shien K, Toyooka S, Ichimura K, et al. Prognostic impact of cancer stem cell-related markers in non-small cell lung cancer patients treated with induction chemoradiotherapy. Lung Cancer 2012;77:162-7
   PubMed Web of Science ®Google Scholar
• Alamgeer M, Peacock CD, Matsui W, et al. Cancer stem cells in lung cancer: evidence and controversies. Respirology 2013;18:757-64
   PubMed Web of Science ®Google Scholar
• Gottschling S, Schnabel PA, Herth FJ, et al. Are we missing the target? Cancer stem cells and drug resistance in non-small cell lung cancer. Cancer Genomics Proteomics 2012;9:275-86
   PubMedGoogle Scholar
• Shimada Y, Saji H, Nomura M, et al. Cancer stem cell-related marker expression in lung adenocarcinoma and relevance of histologic subtypes based on IASLC/ATS/ERS classification. Onco Targets Ther 2013;6:1597-604
   PubMed Web of Science ®Google Scholar
• Tetsuya M. Molecular epidemiology of lung cancer and geographic variations with special reference to EGFR mutations. Transl Lung Cancer Res 2014;3:205-11
   Google Scholar
• Cortes-Funes H, Gomez C, Rosell R, et al. Epidermal growth factor receptor activating mutations in Spanish gefitinib-treated non-small-cell lung cancer patients. Ann Oncol 2005;16:1081-6
   PubMed Web of Science ®Google Scholar
• Bauml J, Mick R, Zhang Y, et al. Frequency of EGFR and KRAS mutations in patients with non-small cell lung cancer by racial background: do disparities exist? Lung Cancer 2013;81:347-53
   Google Scholar
• Sun PL, Seol H, Lee HJ, et al. High incidence of EGFR mutations in Korean men smokers with no intratumoral heterogeneity of lung adenocarcinomas: correlation with histologic subtypes, EGFR/TTF-1 expressions, and clinical features. J Thorac Oncol 2012;7:323-30
   PubMed Web of Science ®Google Scholar
• Sahoo R, Harini VV, Babu VC, et al. Screening for EGFR mutations in lung cancer, a report from India. Lung Cancer 2011;73:316-19
   PubMedGoogle Scholar
• Arrieta O, Cardona AF, Martín C, et al. Updated Frequency of EGFR and KRAS Mutations in NonSmall-Cell Lung Cancer in Latin America: The Latin-American Consortium for the Investigation of Lung Cancer (CLICaP). J Thorac Oncol 2015;10:838-43
   PubMed Web of Science ®Google Scholar
• Jin G, Kim MJ, Jeon HS, et al. PTEN mutations and relationship to EGFR, ERBB2, KRAS, and TP53 mutations in non-small cell lung cancers. Lung Cancer 2010;69:279-83
   PubMed Web of Science ®Google Scholar
• Maus MK, Grimminger PP, Mack PC, et al. KRAS mutations in non-small-cell lung cancer and colorectal cancer: implications for EGFR-targeted therapies. Lung Cancer 2014;83:163-7
   Google Scholar
• Lee HY, Ahn HK, Jeong JY, et al. Favorable clinical outcomes of pemetrexed treatment in anaplastic lymphoma kinase positive non-small-cell lung cancer. Lung Cancer 2013;79:40-5
   Google Scholar
• Gadgeel SM, Chen W, Cote ML, et al. Fibroblast growth factor receptor 1 amplification in non-small cell lung cancer by quantitative real-time PCR. PLoS One 2013;8:e79820
   Google Scholar
• Tran TN, Selinger CI, Kohonen-Corish MR, et al. Fibroblast growth factor receptor 1 (FGFR1) copy number is an independent prognostic factor in non-small cell. Lung Cancer. Lung Cancer 2013;81:462-7
   PubMed Web of Science ®Google Scholar
• Wang L, Hu H, Pan Y, et al. PIK3CA Mutations Frequently Coexist with EGFR/KRAS Mutations in Non-Small Cell Lung Cancer and Suggest Poor Prognosis in EGFR/KRAS Wildtype Subgroup. PLoS One 2014;9:e88291
   PubMed Web of Science ®Google Scholar
• Tomizawa K, Suda K, Onozato R, et al. Prognostic and predictive implications of HER2/ERBB2/neu gene mutations in lung cancers. Lung Cancer 2011;74:139-44
   PubMed Web of Science ®Google Scholar
• Bergethon K, Shaw AT, Ou SH, et al. ROS1 rearrangements define a unique molecular class of lung cancer. J Clin Oncol 2012;30:863-70
   PubMed Web of Science ®Google Scholar
• Sasaki H, Hikosaka Y, Kawano O, et al. MEK1 and AKT2 mutations in Japanese lung cancer. J Thorac Oncol 2010;5:597-600
   Google Scholar
• Li CH, Chen Y. Targeting long non-coding RNAs in cancers: progress and prospects. Int J Biochem Cell Biol 2013;45:1895-910
   PubMed Web of Science ®Google Scholar