Tuberc Respir Dis.  2014 Aug;77(2):49-54. 10.4046/trd.2014.77.2.49.

Molecular Pathology of Lung Cancer: Current Status and Future Directions

  • 1Department of Pathology, Dong-A University College of Medicine, Busan, Korea.


The rapid development of targeted therapies has enormously changed the clinical management of lung cancer patients over the past decade; therefore, molecular testing, such as epidermal growth factor receptor (EGFR) gene mutations or anaplastic lymphoma kinase (ALK) gene rearrangements, is now routinely used to predict the therapeutic responses in lung cancer patients. Moreover, as technology and knowledge supporting molecular testing is rapidly evolving, the landscape of targetable genomic alterations in lung cancer is expanding as well. This article will summarize the current state of the most commonly altered and most clinically relevant genes in lung cancer along with a brief review of potential future developments in molecular testing of lung cancer.


Lung Neoplasms; Biological Markers; Molecular Diagnostic Techniques

MeSH Terms

Gene Rearrangement
Lung Neoplasms*
Molecular Diagnostic Techniques
Pathology, Molecular*
Receptor, Epidermal Growth Factor
Receptor, Epidermal Growth Factor

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1. Lindeman NI, Cagle PT, Beasley MB, Chitale DA, Dacic S, Giaccone G, 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. J Thorac Oncol. 2013; 8:823–859.
2. Thunnissen E, van der Oord K, den Bakker M. Prognostic and predictive biomarkers in lung cancer. A review. Virchows Arch. 2014; 464:347–358.
3. Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA, Brannigan BW, 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; 350:2129–2139.
4. Mok TS, Wu YL, Thongprasert S, Yang CH, Chu DT, Saijo N, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009; 361:947–957.
5. Sequist LV, Yang JC, Yamamoto N, O'Byrne K, Hirsh V, Mok T, et al. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol. 2013; 31:3327–3334.
6. Soda M, Choi YL, 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. 2007; 448:561–566.
7. Shaw AT, Kim DW, Nakagawa K, Seto T, Crino L, Ahn MJ, et al. Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N Engl J Med. 2013; 368:2385–2394.
8. Dacic S, Nikiforova MN. Present and future molecular testing of lung carcinoma. Adv Anat Pathol. 2014; 21:94–99.
9. Shames DS, Wistuba II. The evolving genomic classification of lung cancer. J Pathol. 2014; 232:121–133.
10. Cagle PT, Allen TC, Olsen RJ. Lung cancer biomarkers: present status and future developments. Arch Pathol Lab Med. 2013; 137:1191–1198.
11. Cooper WA, Lam DC, O'Toole SA, Minna JD. Molecular biology of lung cancer. J Thorac Dis. 2013; 5:Suppl 5. S479–S490.
12. Bentley DR, Balasubramanian S, Swerdlow HP, Smith GP, Milton J, Brown CG, et al. Accurate whole human genome sequencing using reversible terminator chemistry. Nature. 2008; 456:53–59.
13. Summerer D. Enabling technologies of genomic-scale sequence enrichment for targeted high-throughput sequencing. Genomics. 2009; 94:363–368.
14. Glenn TC. Field guide to next-generation DNA sequencers. Mol Ecol Resour. 2011; 11:759–769.
15. Prenzel N, Fischer OM, Streit S, Hart S, Ullrich A. The epidermal growth factor receptor family as a central element for cellular signal transduction and diversification. Endocr Relat Cancer. 2001; 8:11–31.
16. Dearden S, Stevens J, Wu YL, Blowers D. Mutation incidence and coincidence in non small-cell lung cancer: meta-analyses by ethnicity and histology (mutMap). Ann Oncol. 2013; 24:2371–2376.
17. Pao W, Miller VA, Politi KA, Riely GJ, Somwar R, Zakowski MF, 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:e73.
18. Takeuchi K, Choi YL, Togashi Y, Soda M, Hatano S, Inamura K, et al. KIF5B-ALK, a novel fusion oncokinase identified by an immunohistochemistry-based diagnostic system for ALK-positive lung cancer. Clin Cancer Res. 2009; 15:3143–3149.
19. Bergethon K, Shaw AT, Ou SH, Katayama R, Lovly CM, McDonald NT, et al. ROS1 rearrangements define a unique molecular class of lung cancers. J Clin Oncol. 2012; 30:863–870.
20. Kohno T, Ichikawa H, Totoki Y, Yasuda K, Hiramoto M, Nammo T, et al. KIF5B-RET fusions in lung adenocarcinoma. Nat Med. 2012; 18:375–377.
21. Marchetti A, Felicioni L, Malatesta S, Grazia Sciarrotta M, Guetti L, Chella A, et al. Clinical features and outcome of patients with non-small-cell lung cancer harboring BRAF mutations. J Clin Oncol. 2011; 29:3574–3579.
22. Sadiq AA, Salgia R. MET as a possible target for non-small-cell lung cancer. J Clin Oncol. 2013; 31:1089–1096.
23. Engelman JA, Zejnullahu K, Mitsudomi T, Song Y, Hyland C, Park JO, et al. MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science. 2007; 316:1039–1043.
24. Mazieres J, Peters S, Lepage B, Cortot AB, Barlesi F, Beau-Faller M, et al. Lung cancer that harbors an HER2 mutation: epidemiologic characteristics and therapeutic perspectives. J Clin Oncol. 2013; 31:1997–2003.
25. Dutt A, Ramos AH, Hammerman PS, Mermel C, Cho J, Sharifnia T, et al. Inhibitor-sensitive FGFR1 amplification in human non-small cell lung cancer. PLoS One. 2011; 6:e20351.
26. Spoerke JM, O'Brien C, Huw L, Koeppen H, Fridlyand J, Brachmann RK, et al. Phosphoinositide 3-kinase (PI3K) pathway alterations are associated with histologic subtypes and are predictive of sensitivity to PI3K inhibitors in lung cancer preclinical models. Clin Cancer Res. 2012; 18:6771–6783.
27. Abdulkareem IH, Blair M. Phosphatase and tensin homologue deleted on chromosome 10. Niger Med J. 2013; 54:79–86.
28. Takeda H, Takigawa N, Ohashi K, Minami D, Kataoka I, Ichihara E, et al. Vandetanib is effective in EGFR-mutant lung cancer cells with PTEN deficiency. Exp Cell Res. 2013; 319:417–423.
29. Hammerman PS, Sos ML, Ramos AH, Xu C, Dutt A, Zhou W, et al. Mutations in the DDR2 kinase gene identify a novel therapeutic target in squamous cell lung cancer. Cancer Discov. 2011; 1:78–89.
30. Travis WD, Brambilla E, Noguchi M, Nicholson AG, Geisinger KR, Yatabe Y, 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; 6:244–285.
31. Shim HS, Chung JH, Kim L, Chang S, Kim WS, Lee GK, et al. Guideline recommendations for EGFR mutation testing in lung cancer: proposal of the Korean Cardiopulmonary Pathology Study Group. Korean J Pathol. 2013; 47:100–106.
32. Kim H, Shim HS, Kim L, Kim TJ, Kwon KY, Lee GK, 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.
33. Thomas A, Rajan A, Lopez-Chavez A, Wang Y, Giaccone G. From targets to targeted therapies and molecular profiling in non-small cell lung carcinoma. Ann Oncol. 2013; 24:577–585.
34. Persson K, Hamby K, Ugozzoli LA. Four-color multiplex reverse transcription polymerase chain reaction--overcoming its limitations. Anal Biochem. 2005; 344:33–42.
35. Cancer Genome Atlas Research Network. Weinstein JN, Collisson EA, Mills GB, Shaw KR, Ozenberger BA, et al. The Cancer Genome Atlas Pan-Cancer analysis project. Nat Genet. 2013; 45:1113–1120.
36. Imielinski M, Berger AH, Hammerman PS, Hernandez B, Pugh TJ, Hodis E, et al. Mapping the hallmarks of lung adenocarcinoma with massively parallel sequencing. Cell. 2012; 150:1107–1120.
37. Cancer Genome Atlas Research Network. Comprehensive genomic characterization of squamous cell lung cancers. Nature. 2012; 489:519–525.
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