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Diagnostic Pathology

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Open Access 01-12-2019 | NSCLC | Research

Analysis of the frequency of oncogenic driver mutations and correlation with clinicopathological characteristics in patients with lung adenocarcinoma from Northeastern Switzerland

Authors: Alexandra Grosse, Claudia Grosse, Markus Rechsteiner, Alex Soltermann

Published in: Diagnostic Pathology | Issue 1/2019

Abstract

Background

Molecular testing of lung adenocarcinoma for oncogenic driver mutations has become standard in pathology practice. The aim of the study was to analyze the EGFR, KRAS, ALK, RET, ROS1, BRAF, ERBB2, MET and PIK3CA mutational status in a representative cohort of Swiss patients with lung adenocarcinoma and to correlate the mutational status with clinicopathological patient characteristics.

Methods

All patients who underwent molecular testing of newly diagnosed lung adenocarcinoma during a 4-year period (2014–2018) were included. Molecular analyses were performed with Sanger sequencing (n = 158) and next generation sequencing (n = 311). ALK, ROS1 and RET fusion gene analyses were also performed with fluorescence in situ hybridization and immunohistochemistry/immunocytochemistry. Demographic and clinical data were obtained from the medical records.

Results

Of 469 patients with informative EGFR mutation analyses, 90 (19.2%) had EGFR mutations. KRAS mutations were present in 33.9% of the patients, while 6.0% of patients showed ALK rearrangement. BRAF, ERBB2, MET and PIK3CA mutations and ROS1 and RET rearrangements were found in 2.6%, 1.9%, 1.9%, 1.5%, 1.7% and 0.8% of the patients, respectively. EGFR mutation was significantly associated with female gender and never smoking status. ALK translocations were more frequent in never smokers, while KRAS mutations were more commonly found in ever smokers. The association between KRAS mutational status and female gender was statistically significant only on multivariate analysis after adjusting for smoking.

Conclusion

The EGFR mutation rate in the current study is among the higher previously reported mutation rates, while the frequencies of KRAS, BRAF, ERBB2 and PIK3CA mutations and ALK, ROS1 and RET rearrangements are similar to the results of previous reports. EGFR and KRAS mutations were significantly associated with gender and smoking. ALK rearrangements showed a significant association with smoking status alone.

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Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394–424. https://doi.org/10.3322/caac.21492.CrossRefPubMed

Jing C, Mao X, Wang Z, Sun K, Ma R, Wu J, et al. Next-generation sequencing-based detection of EGFR, KRAS, BRAF, NRAS, PIK3CA, Her-2 and TP53 mutations in patients with non-small cell lung cancer. Mol Med Rep. 2018;18:2191–7. https://doi.org/10.3892/mmr.2018.9210.CrossRefPubMedPubMedCentral

Zhao F, Xu M, Lei H, Zhou Z, Wang L, Li P, et al. Clinicopathological characteristics of patients with non-small-cell lung cancer who harbor EML4-ALK fusion gene: a meta-analysis. PLoS One. 2015;10:e0117333. https://doi.org/10.1371/journal.pone.0117333.CrossRefPubMedPubMedCentral

Gkolfinopoulos S, Mountzios G. Beyond EGFR and ALK: targeting rare mutations in advanced non-small cell lung cancer. Ann Transl Med. 2018;6:142. https://doi.org/10.21037/atm.2018.04.28.CrossRefPubMedPubMedCentral

Ess SM, Herrmann C, Frick H, Krapf M, Cerny T, Jochum W, et al. Epidermal growth factor receptor and anaplastic lymphoma kinase testing and mutation prevalence in patients with advanced non-small cell lung cancer in Switzerland: a comprehensive evaluation of real world practices. Eur J Cancer Care. 2017;26:e12721. https://doi.org/10.1111/ecc.12721.CrossRef

Schwegler C, Kaufmann D, Pfeiffer D, Aebi S, Diebold J, Gautschi O. Population-level effect of molecular testing and targeted therapy in patients with advanced pulmonary adenocarcinoma: a prospective cohort study. Virchows Arch. 2018;472:581–8. https://doi.org/10.1007/s00428-017-2268-y.CrossRefPubMed

Arndt V, Feller A, Hauri D, Heusser R, Junker C, Kuehni C, Lorez M, Pfeiffer V, Roy E, Schindler M. Swiss cancer report 2015. Neuchatel: Federal Statistical Office; 2016.

Oberli LS, Valeri F, Korol D, Rohrmann S, Dehler S. 31 years of lung cancer in the canton of Zurich, Switzerland: incidence trends by sex, histology and laterality. Swiss Med Wkly. 2016;146:w14327. https://doi.org/10.4414/smw.2016.14327.CrossRefPubMed

Lorez M, Rohrmann S, Heusser R, Volker A, NICER Working Group. Lung cancer trends by histologic subtype in Switzerland: Schweizer Krebsbulletin. 2017;37:179–85.

10.

Brierley JD, Gospodarowicz MK, Wittekind C, editors. TNM classification of malignant tumours. UK: John Wiley & Sons, Ltd; 2017.

11.

Velizheva NP, Rechsteiner MP, Valtcheva N, Freiberger SN, Wong CE, Vrugt B, et al. Targeted next-generation-sequencing for reliable detection of targetable rearrangements in lung adenocarcinoma – a single center retrospective study. Pathol Res Pract. 2018;214:572–8. https://doi.org/10.1016/j.prp.2018.02.001.CrossRefPubMedPubMedCentral

12.

Velizheva NP, Rechsteiner MP, Wong CE, Zhong Q, Rössle M, Bode B, et al. Cytology smears as excellent starting material for next-generation sequencing-based molecular testing of patients with adenocarcinoma of the lung. Cancer Cytopathol. 2017;125:30–40. https://doi.org/10.1002/cncy.21771.CrossRefPubMed

13.

Brcic L, Jakopovic M, Misic M, Seiwerth F, Kern I, Smojver-Jezek S, et al. Analysis of the frequency of EGFR, KRAS and ALK mutations in patients with lung adenocarcinoma in Croatia. Diagn Pathol. 2016;11:90. https://doi.org/10.1186/s13000-016-0544-9.CrossRefPubMedPubMedCentral

14.

Ramlau R, Cufer T, Berzinec P, Dziadziuszko R, Olszewski W, Popper H, et al. Epidermal growth factor receptor mutation-positive non-small-cell lung cancer in the real-world setting in Central Europe: the INSIGHT study. J Thorac Oncol. 2015;10:1370–4. https://doi.org/10.1097/JTO.0000000000000621.CrossRefPubMed

15.

Milella M, Nuzzo C, Bria E, Sperduti I, Visca P, Buttitta F, et al. EGFR molecular profiling in advanced NSCLC: a prospective phase II study in molecularly/clinically selected patients pretreated with chemotherapy. J Thorac Oncol. 2012;7:672–80. https://doi.org/10.1097/JTO.0b013e31824a8bde.CrossRefPubMed

16.

Zaric B, Stojsic V, Kovacevic T, Sarcev T, Tepavac A, Jankovic R, et al. Clinical characteristics, tumor, node, metastasis status, and mutation rate in domain of epidermal growth factor receptor gene in serbian patients with lung adenocarcinoma. J Thorac Oncol. 2014;9:1406–10. https://doi.org/10.1097/JTO.0000000000000242.CrossRefPubMed

17.

Helland Å, Skaug HM, Kleinberg L, Iversen ML, Rud AK, Fleischer T, et al. EGFR gene alterations in a Norwegian cohort of lung cancer patients selected for surgery. J Thorac Oncol. 2011;6:947–50. https://doi.org/10.1097/JTO.0b013e31820db209.CrossRefPubMed

18.

Berg J, Fjellbirkeland L, Suhrke P, Jebsen P, Lund-Iversen M, Kleinberg L, et al. EGFR mutation testing of lung cancer patients - experiences from Vestfold hospital trust. Acta Oncol. 2016;55:149–55. https://doi.org/10.3109/0284186X.2015.1062537.CrossRefPubMed

19.

Vallee A, Sagan C, Le Loupp AG, Bach K, Dejoie T, Denis MG. Detection of EGFR gene mutations in non-small cell lung cancer: lessons from a single-institution routine analysis of 1,403 tumor samples. Int J Oncol. 2013;43:1045–51. https://doi.org/10.3892/ijo.2013.2056.CrossRefPubMedPubMedCentral

20.

Moiseyenko VM, Procenko SA, Levchenko EV, Barchuk AS, Moiseyenko FV, Iyevleva AG, et al. High efficacy of first-line gefitinib in non-Asian patients with EGFR-mutated lung adenocarcinoma. Onkologie. 2010;33:231–8. https://doi.org/10.1159/000302729.CrossRefPubMed

21.

Midha A, Dearden S, McCormack R. EGFR mutation incidence in non-small-cell lung cancer of adenocarcinoma histology: a systematic review and global map by ethnicity (mutMapII). Am J Cancer Res. 2015;5:2892–911.PubMedPubMedCentral

22.

Hlinkova K, Babal P, Berzinec P, Majer I, Mikle-Barathova Z, Piackova B, et al. Evaluation of 2-year experience with EGFR mutation analysis of small diagnostic samples. Diagn Mol Pathol. 2013;22:70–5. https://doi.org/10.1097/PDM.0b013e31827e6984.CrossRefPubMed

23.

Bauml J, Mick R, Zhang Y, Watt CD, Vachani A, Aggarwal C, 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. https://doi.org/10.1016/j.lungcan.2013.05.011.CrossRefPubMedPubMedCentral

24.

Xia N, An J, Jiang QQ, Li M, Tan J, Hu CP. Analysis of EGFR, EML4-ALK, KRAS, and c-MET mutations in Chinese lung adenocarcinoma patients. Exp Lung Res. 2013;39:328–35. https://doi.org/10.3109/01902148.2013.819535.CrossRefPubMed

25.

Gao B, Sun Y, Zhang J, Ren Y, Fang R, Han X, et al. Spectrum of LKB1, EGFR, and KRAS mutations in chinese lung adenocarcinomas. J Thorac Oncol. 2010;5:1130–5. https://doi.org/10.1097/JTO.0b013e3181e05016.CrossRefPubMedPubMedCentral

26.

Illei PB, Belchis D, Tseng LH, Nguyen D, De Marchi F, Haley L, et al. Clinical mutational profiling of 1006 lung cancers by next generation sequencing. Oncotarget. 2017;8:96684–96. https://doi.org/10.18632/oncotarget.18042.CrossRefPubMedPubMedCentral

27.

Riely GJ, Kris MG, Rosenbaum D, Marks J, Li A, Chitale DA, et al. Frequency and distinctive spectrum of KRAS mutations in never smokers with lung adenocarcinoma. Clin Cancer Res. 2008;14:5731–4. https://doi.org/10.1158/1078-0432.CCR-08-0646.CrossRefPubMedPubMedCentral

28.

Dogan S, Shen R, Ang DC, Johnson ML, D'Angelo SP, Paik PK, et al. Molecular epidemiology of EGFR and KRAS mutations in 3,026 lung adenocarcinomas: higher susceptibility of women to smoking-related KRAS-mutant cancers. Clin Cancer Res. 2012;18:6169–77. https://doi.org/10.1158/1078-0432.CCR-11-3265.CrossRefPubMedPubMedCentral

29.

Takamochi K, Oh S, Suzuki K. Differences in EGFR and KRAS mutation spectra in lung adenocarcinoma of never and heavy smokers. Oncol Lett. 2013;6:1207–12. https://doi.org/10.3892/ol.2013.1551.CrossRefPubMedPubMedCentral

30.

Bae NC, Chae MH, Lee MH, Kim KM, Lee EB, Kim CH, et al. EGFR, ERBB2, and KRAS mutations in Korean non-small cell lung cancer patients. Cancer Genet Cytogenet. 2007;173:107–13. https://doi.org/10.1016/j.cancergencyto.2006.10.007.CrossRefPubMed

31.

Liu L, Liu J, Shao D, Deng Q, Tang H, Liu Z, et al. Comprehensive genomic profiling of lung cancer using a validated panel to explore therapeutic targets in east Asian patients. Cancer Sci. 2017;108:2487–94. https://doi.org/10.1111/cas.13410.CrossRefPubMedPubMedCentral

32.

Ahrendt SA, Decker PA, Alawi EA, Zhu Yr YR, Sanchez-Cespedes M, Yang SC, et al. Cigarette smoking is strongly associated with mutation of the K-ras gene in patients with primary adenocarcinoma of the lung. Cancer. 2001;92:1525–30.CrossRef

33.

Ferrer I, Zugazagoitia J, Herbertz S, John W, Paz-Ares L, Schmid-Bindert G. KRAS-mutant non-small cell lung cancer: from biology to therapy. Lung Cancer. 2018;124:53–64. https://doi.org/10.1016/j.lungcan.2018.07.013.CrossRefPubMed

34.

Wood K, Hensing T, Malik R, Salgia R. Prognostic and predictive value in KRAS in non-small-cell lung cancer: a review. JAMA Oncol. 2016;2:805–12. https://doi.org/10.1001/jamaoncol.2016.0405.CrossRefPubMed

35.

Jänne PA, Shaw AT, Pereira JR, Jeannin G, Vansteenkiste J, Barrios C, 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;14:38–47. https://doi.org/10.1016/S1470-2045(12)70489-8.CrossRefPubMed

36.

A Study of Abemaciclib (LY2835219) in participants with previously treated KRAS mutated lung cancer (JUNIPER). Avalaible online: https://clinicaltrials.gov/ct2/show/NCT02152631. Accessed 10 Nov 2018.

37.

Bacchi CE, Ciol H, Queiroga EM, Benine LC, Silva LH, Ojopi EB. Epidermal growth factor receptor and KRAS mutations in Brazilian lung cancer patients. Clinics (Sao Paulo). 2012;67:419–24. https://doi.org/papers2://publication/uuid/F04AA1B0-F128-493A-A47B-F45F7553371A

38.

Rouquette I, Lauwers-Cances V, Allera C, Brouchet L, Milia J, Nicaise Y, et al. Characteristics of lung cancer in women: importance of hormonal and growth factors. Lung Cancer. 2012;76:280–5. https://doi.org/10.1016/j.lungcan.2011.11.023.CrossRefPubMed

39.

Kwak EL, Bang YJ, Camidge DR, Shaw AT, Solomon B, Maki RG, et al. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med. 2010;363:1693–703. https://doi.org/10.1056/NEJMoa1006448.CrossRefPubMedPubMedCentral

40.

Takeuchi K, Choi YL, Soda M, Inamura K, Togashi Y, Hatano S, et al. Multiplex reverse transcription-PCR screening for EML4-ALK fusion transcripts. Clin Cancer Res. 2008;14:6618–24. https://doi.org/10.1158/1078-0432.CCR-08-1018.CrossRefPubMed

41.

Wong DW, Leung EL, So KK, Tam IY, Sihoe AD, Cheng LC, et al. The EML4-ALK fusion gene is involved in various histologic types of lung cancers from nonsmokers with wild-type EGFR and KRAS. Cancer. 2009;115:1723–33. https://doi.org/10.1002/cncr.24181.

42.

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;448:561–6. https://doi.org/10.1038/nature05945.CrossRefPubMed

43.

Shinmura K, Kageyama S, Tao H, Bunai T, Suzuki M, Kamo T, et al. EML4-ALK fusion transcripts, but no NPM-, TPM3-, CLTC-, ATIC-, or TFG-ALK fusion transcripts, in non-small cell lung carcinomas. Lung Cancer. 2008;61:163–9. https://doi.org/10.1016/j.lungcan.2007.12.013.CrossRefPubMed

44.

Koivunen JP, Mermel C, Zejnullahu K, Murphy C, Lifshits E, Holmes AJ, et al. EML4-ALK fusion gene and efficacy of an ALK kinase inhibitor in lung cancer. Clin Cancer Res. 2008;14:4275–83. https://doi.org/10.1158/1078-0432.CCR-08-0168.CrossRefPubMedPubMedCentral

45.

Paik JH, Choi CM, Kim H, Jang SJ, Choe G, Kim DK, et al. Clinicopathologic implication of ALK rearrangement in surgically resected lung cancer: a proposal of diagnostic algorithm for ALK-rearranged adenocarcinoma. Lung Cancer. 2012;76:403–9. https://doi.org/10.1016/j.lungcan.2011.11.008.CrossRefPubMed

46.

Pratilas CA, Hanrahan AJ, Halilovic E, Persaud Y, Soh J, Chitale D, et al. Genetic predictors of MEK dependence in non-small cell lung cancer. Cancer Res. 2008;68:9375–83. https://doi.org/10.1158/0008-5472.CAN-08-2223.CrossRefPubMedPubMedCentral

47.

Cardarella S, Ogino A, Nishino M, Butaney M, Shen J, Lydon C, et al. Clinical, pathologic, and biologic features associated with BRAF mutations in non-small cell lung cancer. Clin Cancer Res. 2013;19:4532–40. https://doi.org/10.1158/1078-0432.CCR-13-0657.CrossRefPubMedPubMedCentral

48.

Paik PK, Arcila ME, Fara M, Sima CS, Miller VA, Kris MG, et al. Clinical characteristics of patients with lung adenocarcinomas harboring BRAF mutations. J Clin Oncol. 2011;29:2046–51. https://doi.org/10.1200/JCO.2010.33.1280.

49.

Nikiforov YE. Thyroid carcinoma: molecular pathways and therapeutic targets. Mod Pathol. 2008;21(Suppl 2):S37–43. https://doi.org/10.1038/modpathol.2008.10.CrossRefPubMedPubMedCentral

50.

Gainor JF, Shaw AT. Novel targets in non-small cell lung cancer: ROS1 and RET fusions. Oncologist. 2013;18:865–75. https://doi.org/10.1634/theoncologist.2013-0095.CrossRefPubMedPubMedCentral

51.

Arcila ME, Chaft JE, Nafa K, Roy-Chowdhuri S, Lau C, Zaidinski M, et al. Prevalence, clinicopathologic associations, and molecular spectrum of ERBB2 (HER2) tyrosine kinase mutations in lung adenocarcinomas. Clin Cancer Res. 2012;18:4910–8. https://doi.org/10.1158/1078-0432.CCR-12-0912.CrossRefPubMed

52.

Buttitta F, Barassi F, Fresu G, Felicioni L, Chella A, Paolizzi D, et al. Mutational analysis of the HER2 gene in lung tumors from Caucasian patients: mutations are mainly present in adenocarcinomas with bronchioloalveolar features. Int J Cancer. 2006;119:2586–91. https://doi.org/10.1002/ijc.22143.

53.

Shigematsu H, Takahashi T, Nomura M, Majmudar K, Suzuki M, Lee H, et al. Somatic mutations of the HER2 kinase domain in lung adenocarcinomas. Cancer Res. 2005;65:1642–6. https://doi.org/10.1158/0008-5472.CAN-04-4235.CrossRefPubMed

54.

Frampton GM, Ali SM, Rosenzweig M, Chmielecki J, Lu X, Bauer TM, et al. Activation of MET via diverse exon 14 splicing alterations occurs in multiple tumor types and confers clinical sensitivity to MET inhibitors. Cancer Discov. 2015;5:850–9. https://doi.org/10.1158/2159-8290.CD-15-0285.CrossRefPubMed

55.

Seo JS, Ju YS, Lee WC, Shin JY, Lee JK, Bleazard T, et al. The transcriptional landscape and mutational profile of lung adenocarcinoma. Genome Res. 2012;22:2109–19. https://doi.org/10.1101/gr.145144.112.CrossRefPubMedPubMedCentral

56.

Cancer Genome Atlas Research Network. Comprehensive molecular profiling of lung adenocarcinoma. Nature. 2014;511:543–50. https://doi.org/10.1038/nature13385.CrossRef

57.

Onozato R, Kosaka T, Kuwano H, Sekido Y, Yatabe Y, Mitsudomi T. Activation of MET by gene amplification or by splice mutations deleting the juxtamembrane domain in primary resected lung cancers. J Thorac Oncol. 2009;4:5–11. https://doi.org/10.1097/JTO.0b013e3181913e0e.CrossRefPubMed

58.

Kawano O, Sasaki H, Endo K, Suzuki E, Haneda H, Yukiue H, et al. PIK3CA mutation status in Japanese lung cancer patients. Lung Cancer. 2006;54:209–15. https://doi.org/10.1016/j.lungcan.2006.07.006.CrossRefPubMed

59.

Yamamoto H, Shigematsu H, Nomura M, Lockwood WW, Sato M, Okumura N, et al. PIK3CA mutations and copy number gains in human lung cancers. Cancer Res. 2008;68:6913–21. https://doi.org/10.1158/0008-5472.CAN-07-5084.CrossRefPubMedPubMedCentral

60.

Qian Y, Chai S, Liang Z, Wang Y, Zhou Y, Xu X, et al. KIF5B-RET fusion kinase promotes cell growth by multilevel activation of STAT3 in lung cancer. Mol Cancer. 2014;13:176. https://doi.org/10.1186/1476-4598-13-176.CrossRefPubMedPubMedCentral

61.

Shaw AT, Ou SH, Bang YJ, Camidge DR, Solomon BJ, Salgia R, et al. Crizotinib in ROS1-rearranged non-small-cell lung cancer. N Engl J Med. 2014;371:1963–71. https://doi.org/10.1056/NEJMoa1406766.CrossRefPubMedPubMedCentral

62.

Wang R, Hu H, Pan Y, Li Y, Ye T, Li C, et al. RET fusions define a unique molecular and clinicopathologic subtype of non-small-cell lung cancer. J Clin Oncol. 2012;30:4352–9. https://doi.org/10.1200/JCO.2012.44.1477.CrossRefPubMed

63.

Liu L, Shao X, Gao W, Bai J, Wang R, Huang P, et al. The role of human epidermal growth factor receptor 2 as a prognostic factor in lung cancer: a meta-analysis of published data. J Thorac Oncol. 2010;5:1922–32.CrossRef

64.

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;18:6771–83. https://doi.org/10.1158/1078-0432.CCR-12-2347.CrossRefPubMed

65.

Zhang L, Shi L, Zhao X, Wang Y, Yue W. PIK3CA gene mutation associated with poor prognosis of lung adenocarcinoma. Onco Targets Ther. 2013;6:497–502. https://doi.org/10.2147/OTT.S41643.CrossRefPubMedPubMedCentral

66.

Chaft JE, Arcila ME, Paik PK, Lau C, Riely GJ, Pietanza MC, et al. Coexistence of PIK3CA and other oncogene mutations in lung adenocarcinoma-rationale for comprehensive mutation profiling. Mol Cancer Ther. 2012;11:485–91. https://doi.org/10.1158/1535-7163.MCT-11-0692.CrossRefPubMed

67.

Wang L, Hu H, Pan Y, Wang R, Li Y, Shen L, 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. https://doi.org/10.1371/journal.pone.0088291.CrossRefPubMedPubMedCentral

68.

Lee GD, Lee SE, Oh DY, Yu DB, Jeong HM, Kim J, et al. MET exon 14 skipping mutations in lung adenocarcinoma: clinicopathologic implications and prognostic values. J Thorac Oncol. 2017;12:1233–46. https://doi.org/10.1016/j.jtho.2017.04.031.CrossRefPubMed

69.

Awad MM, Oxnard GR, Jackman DM, Savukoski DO, Hall D, Shivdasani P, et al. MET exon 14 mutations in non-small-cell lung cancer are associated with advanced age and stage-dependent MET genomic amplification and c-met overexpression. J Clin Oncol. 2016;34:721–30. https://doi.org/10.1200/JCO.2015.63.4600.CrossRefPubMed

70.

Zheng D, Wang R, Ye T, Yu S, Hu H, Shen X, et al. MET exon 14 skipping defines a unique molecular class of non-small cell lung cancer. Oncotarget. 2016;7:41691–702. https://doi.org/10.18632/oncotarget.9541.CrossRefPubMedPubMedCentral

Title: Analysis of the frequency of oncogenic driver mutations and correlation with clinicopathological characteristics in patients with lung adenocarcinoma from Northeastern Switzerland
Authors: Alexandra Grosse
Claudia Grosse
Markus Rechsteiner
Alex Soltermann
Publication date: 01-12-2019
Publisher: BioMed Central
Keywords: NSCLC
NSCLC
Published in: Diagnostic Pathology / Issue 1/2019
Electronic ISSN: 1746-1596
DOI: https://doi.org/10.1186/s13000-019-0789-1

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Analysis of the frequency of oncogenic driver mutations and correlation with clinicopathological characteristics in patients with lung adenocarcinoma from Northeastern Switzerland

Abstract

Background

Methods

Results

Conclusion

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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