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BMC Cancer
Published in: BMC Cancer 1/2014

Open Access 01-12-2014 | Research article

Prospective genetic profiling of squamous cell lung cancer and adenosquamous carcinoma in Japanese patients by multitarget assays

Authors: Hirotsugu Kenmotsu, Masakuni Serizawa, Yasuhiro Koh, Mitsuhiro Isaka, Toshiaki Takahashi, Tetsuhiko Taira, Akira Ono, Tomohiro Maniwa, Shoji Takahashi, Keita Mori, Masahiro Endo, Masato Abe, Isamu Hayashi, Takashi Nakajima, Yasuhisa Ohde, Nobuyuki Yamamoto

Published in: BMC Cancer | Issue 1/2014

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Abstract

Background

Despite considerable recent progress in the treatment of lung adenocarcinoma, there has been little progress in the development of efficacious molecular targeted therapies for squamous cell lung cancer. In addition to the recent comprehensive genome-wide characterization of squamous cell lung cancer, it is also important to genotype this form of cancer. We therefore conducted the Shizuoka Lung Cancer Mutation Study to analyze driver mutations in patients with thoracic malignancies. Here we report the results of genotyping in patients with squamous cell lung cancer.

Methods

Based on the biobanking system, in conjunction with the clinic and pathology lab, we developed a genotyping panel designed to assess 24 mutations in 10 genes (EGFR, KRAS, BRAF, PIK3CA, NRAS, MEK1, AKT1, PTEN, HER2 and DDR2), EGFR, MET, PIK3CA, FGFR1 and FGFR2 copy numbers, and EML4-ALK and ROS1 translocations, using pyrosequencing plus capillary electrophoresis, quantitative polymerase chain reaction (PCR) and reverse-transcription PCR, respectively.

Results

A total of 129 patients with squamous cell lung cancer and adenosquamous carcinoma were enrolled in this study between July 2011 and November 2012. We detected genetic alterations in 40% of all cases. Gene alterations included: EGFR mutations, 6%; KRAS mutations, 4%; PIK3CA mutations, 13%; NRAS mutations, 1%; KIF5b-RET fusion gene, 1%; EGFR copy number gain, 5%; PIK3CA copy number gain, 15%; and FGFR1 copy number gain, 5%. Twelve patients (9%) harbored simultaneous genetic alterations. Genetic alterations were detected more frequently in surgically-resected, snap-frozen samples than in formalin-fixed, paraffin-embedded samples (50% vs. 29%). In addition, patients aged ≤70 years old and never-smokers showed high frequencies of genetic alterations.

Conclusions

This study represents one of the largest prospective tumor-genotyping studies to be performed in Asian patients with squamous cell lung cancer. These results suggest that incorporation of genetic profiling into lung cancer clinical practice may facilitate the administration of personalized cancer treatments in patients with squamous cell lung cancer.
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Literature
1.
Scagliotti GV, Parikh P, von Pawel J, Biesma B, Vansteenkiste J, Manegold C, Serwatowski P, Gatzemeier U, Digumarti R, Zukin M, Lee JS, Mellemgaard A, Park K, Patil S, Rolski J, Goksel T, de Marinis F, Simms L, Sugarman KP, Gandara D: Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. J Clin Oncol. 2008, 26 (21): 3543-3551. 10.1200/JCO.2007.15.0375.CrossRefPubMed
2.
Sandler A, Gray R, Perry MC, Brahmer J, Schiller JH, Dowlati A, Lilenbaum R, Johnson DH: Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med. 2006, 355 (24): 2542-2550. 10.1056/NEJMoa061884.CrossRefPubMed
3.
Mok TS, Wu YL, Thongprasert S, Yang CH, Chu DT, Saijo N, Sunpaweravong P, Han B, Margono B, Ichinose Y, Nishiwaki Y, Ohe Y, Yang JJ, Chewaskulyong B, Jiang H, Duffield EL, Watkins CL, Armour AA, Fukuoka M: Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009, 361 (10): 947-957. 10.1056/NEJMoa0810699.CrossRefPubMed
4.
Maemondo M, Inoue A, Kobayashi K, Sugawara S, Oizumi S, Isobe H, Gemma A, Harada M, Yoshizawa H, Kinoshita I, Fujita Y, Okinaga S, Hirano S, Yoshimori K, Harada T, Ogura T, Ando M, Miyazawa H, Tanaka T, Saijo Y, Hagiwara K, Morita S, Nukiwa T: Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med. 2010, 362 (25): 2380-2388. 10.1056/NEJMoa0909530.CrossRefPubMed
5.
Mitsudomi T, Morita S, Yatabe Y, Negoro S, Okamoto I, Tsurutani J, Seto T, Satouchi M, Tada H, Hirashima T, Asami K, Katakami N, Takada M, Yoshioka H, Shibata K, Kudoh S, Shimizu E, Saito S, Toyooka S, Nakagawa K, Fukuoka M: 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): 121-128. 10.1016/S1470-2045(09)70364-X.CrossRefPubMed
6.
Kwak EL, Bang YJ, Camidge DR, Shaw AT, Solomon B, Maki RG, Ou SH, Dezube BJ, Janne PA, Costa DB, Varella-Garcia M, Kim WH, Lynch TJ, Fidias P, Stubbs H, Engelman JA, Sequist LV, Tan W, Gandhi L, Mino-Kenudson M, Wei GC, Shreeve SM, Ratain MJ, Settleman J, Christensen JG, Haber DA, Wilner K, Salgia R, Shapiro GI, Clark JW, et al. : Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med. 2010, 363 (18): 1693-1703. 10.1056/NEJMoa1006448.CrossRefPubMedPubMedCentral
7.
Shaw AT, Kim DW, Nakagawa K, Seto T, Crino L, Ahn MJ, De Pas T, Besse B, Solomon BJ, Blackhall F, Wu YL, Thomas M, O'Byrne KJ, Moro-Sibilot D, Camidge DR, Mok T, Hirsh V, Riely GJ, Iyer S, Tassell V, Polli A, Wilner KD, Janne PA: Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N Engl J Med. 2013, 368 (25): 2385-2394. 10.1056/NEJMoa1214886.CrossRefPubMed
8.
Comprehensive genomic characterization of squamous cell lung cancers. Nature. 2012, 489 (7417): 519-525. 10.1038/nature11404.
9.
Paik PK, Hasanovic A, Wang L, Rekhtman N, Ladanyi M, Kris MG: Multiplex testing for driver mutations in squamous cell carcinomas of the lung. ASCO Meeting Abstracts. 2012, 30 (15_suppl): 7505-
10.
Kim Y, Hammerman PS, Kim J, Yoon JA, Lee Y, Sun JM, Wilkerson MD, Pedamallu CS, Cibulskis K, Yoo YK, Lawrence MS, Stojanov P, Carter SL, McKenna A, Stewart C, Sivachenko AY, Oh IJ, Kim HK, Choi YS, Kim K, Shim YM, Kim KS, Song SY, Na KJ, Choi YL, Hayes DN, Cho S, Kim YC, Ahn JS, Ahn MJ, et al. : Integrative and comparative genomic analysis of lung squamous cell carcinomas in East asian patients. J Clin Oncol. 2014, 32 (2): 121-128. 10.1200/JCO.2013.50.8556.CrossRefPubMed
11.
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 (9): 2371-2376. 10.1093/annonc/mdt205.CrossRefPubMedPubMedCentral
12.
Pao W, Girard N: New driver mutations in non-small-cell lung cancer. Lancet Oncol. 2011, 12 (2): 175-180. 10.1016/S1470-2045(10)70087-5.CrossRefPubMed
13.
Oxnard GR, Binder A, Janne PA: New targetable oncogenes in non-small-cell lung cancer. J Clin Oncol. 2013, 31 (8): 1097-1104. 10.1200/JCO.2012.42.9829.CrossRefPubMedPubMedCentral
14.
Gadgeel SM: New targets in non-small cell lung cancer. Curr Oncol Rep. 2013, 15 (4): 411-423. 10.1007/s11912-013-0326-4.CrossRefPubMed
15.
Su Z, Dias-Santagata D, Duke M, Hutchinson K, Lin YL, Borger DR, Chung CH, Massion PP, Vnencak-Jones CL, Iafrate AJ, Pao W: A platform for rapid detection of multiple oncogenic mutations with relevance to targeted therapy in non-small-cell lung cancer. J Mol Diagn. 2011, 13 (1): 74-84. 10.1016/j.jmoldx.2010.11.010.CrossRefPubMedPubMedCentral
16.
Serizawa M, Koh Y, Kenmotsu H, Isaka M, Murakami H, Akamatsu H, Mori K, Abe M, Hayashi I, Taira T, Maniwa T, Takahashi T, Endo M, Nakajima T, Ohde Y, Yamamoto N: Assessment of mutational profile of Japanese lung adenocarcinoma patients by multitarget assays: a prospective single-institute study. Cancer. 2014, 120 (10): 1471-1481.CrossRefPubMed
17.
Ross JS, Cronin M: Whole cancer genome sequencing by next-generation methods. Am J Clin Pathol. 2011, 136 (4): 527-539. 10.1309/AJCPR1SVT1VHUGXW.CrossRefPubMed
18.
Khuder SA: Effect of cigarette smoking on major histological types of lung cancer: a meta-analysis. Lung Cancer. 2001, 31 (2–3): 139-148.CrossRefPubMed
19.
Moses W, Weng J, Khanafshar E, Duh QY, Clark OH, Kebebew E: Multiple genetic alterations in papillary thyroid cancer are associated with younger age at presentation. J Surg Res. 2010, 160 (2): 179-183. 10.1016/j.jss.2009.05.031.CrossRefPubMed
20.
Onozato W, Yamashita K, Kuba T, Katoh H, Nakamura T, Sato T, Ihara A, Okayasu I, Watanabe M: Genetic alterations of K-ras may reflect prognosis in stage III colon cancer patients below 60 years of age. J Surg Oncol. 2011, 103 (1): 25-33. 10.1002/jso.21710.CrossRefPubMed
21.
Ueno T, Toyooka S, Suda K, Soh J, Yatabe Y, Miyoshi S, Matsuo K, Mitsudomi T: Impact of age on epidermal growth factor receptor mutation in lung cancer. Lung Cancer. 2012, 78 (3): 207-211. 10.1016/j.lungcan.2012.09.006.CrossRefPubMed
22.
Liu D, Hou P, Liu Z, Wu G, Xing M: Genetic alterations in the phosphoinositide 3-kinase/Akt signaling pathway confer sensitivity of thyroid cancer cells to therapeutic targeting of Akt and mammalian target of rapamycin. Cancer Res. 2009, 69 (18): 7311-7319. 10.1158/0008-5472.CAN-09-1077.CrossRefPubMedPubMedCentral
23.
Yamamoto H, Shigematsu H, Nomura M, Lockwood WW, Sato M, Okumura N, Soh J, Suzuki M, Wistuba II, Fong KM, Lee H, Toyooka S, Date H, Lam WL, Minna JD, Gazdar AF: PIK3CA mutations and copy number gains in human lung cancers. Cancer Res. 2008, 68 (17): 6913-6921. 10.1158/0008-5472.CAN-07-5084.CrossRefPubMedPubMedCentral
24.
Kawano O, Sasaki H, Endo K, Suzuki E, Haneda H, Yukiue H, Kobayashi Y, Yano M, Fujii Y: PIK3CA mutation status in Japanese lung cancer patients. Lung Cancer. 2006, 54 (2): 209-215. 10.1016/j.lungcan.2006.07.006.CrossRefPubMed
25.
Koh Y, Kenmotsu H, Serizawa M, Isaka M, Mori K, Imai H, Akamatsu H, Ono A, Naito T, Taira T, Murakami H, Takahashi T, Endo M, Nakajima T, Ohde Y, Yamamoto N: Identification of actionable mutations in surgically resected tumor specimens from Japanese patients with non-small cell lung cancer by ultra-deep targeted sequencing. ASCO Meeting Abstracts. 2013, 31 (15_suppl): 7572-
26.
Brooks AN, Kilgour E, Smith PD: Molecular pathways: fibroblast growth factor signaling: a new therapeutic opportunity in cancer. Clin Cancer Res. 2012, 18 (7): 1855-1862. 10.1158/1078-0432.CCR-11-0699.CrossRefPubMed
27.
Drilon A, Rekhtman N, Ladanyi M, Paik P: Squamous-cell carcinomas of the lung: emerging biology, controversies, and the promise of targeted therapy. Lancet Oncol. 2012, 13 (10): e418-e426. 10.1016/S1470-2045(12)70291-7.CrossRefPubMed
28.
Heist RS, Mino-Kenudson M, Sequist LV, Tammireddy S, Morrissey L, Christiani DC, Engelman JA, Iafrate AJ: FGFR1 amplification in squamous cell carcinoma of the lung. J Thorac Oncol. 2012, 7 (12): 1775-1780. 10.1097/JTO.0b013e31826aed28.CrossRefPubMedPubMedCentral
29.
Sasaki H, Shitara M, Yokota K, Hikosaka Y, Moriyama S, Yano M, Fujii Y: Increased FGFR1 copy number in lung squamous cell carcinomas. Mol Med Rep. 2012, 5 (3): 725-728.PubMed
30.
Kim HR, Kim DJ, Kang DR, Lee JG, Lim SM, Lee CY, Rha SY, Bae MK, Lee YJ, Kim SH, Ha SJ, Soo RA, Chung KY, Kim JH, Lee JH, Shim HS, Cho BC: 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 (6): 731-737. 10.1200/JCO.2012.43.8622.CrossRefPubMed
31.
Gerlinger M, Rowan AJ, Horswell S, Larkin J, Endesfelder D, Gronroos E, Martinez P, Matthews N, Stewart A, Tarpey P, Varela I, Phillimore B, Begum S, McDonald NQ, Butler A, Jones D, Raine K, Latimer C, Santos CR, Nohadani M, Eklund AC, Spencer-Dene B, Clark G, Pickering L, Stamp G, Gore M, Szallasi Z, Downward J, Futreal PA, Swanton C: Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med. 2012, 366 (10): 883-892. 10.1056/NEJMoa1113205.CrossRefPubMedPubMedCentral
Metadata
Title
Prospective genetic profiling of squamous cell lung cancer and adenosquamous carcinoma in Japanese patients by multitarget assays
Authors
Hirotsugu Kenmotsu
Masakuni Serizawa
Yasuhiro Koh
Mitsuhiro Isaka
Toshiaki Takahashi
Tetsuhiko Taira
Akira Ono
Tomohiro Maniwa
Shoji Takahashi
Keita Mori
Masahiro Endo
Masato Abe
Isamu Hayashi
Takashi Nakajima
Yasuhisa Ohde
Nobuyuki Yamamoto
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2014
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-14-786

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