CD74-ROS1 fusion transcripts in resected non-small cell lung carcinoma

Matsuura,Shun; Shinmura,Kazuya; Kamo,Takaharu; Igarashi,Hisaki; Maruyama,Kyoko; Tajima,Mari; Ogawa,Hiroshi; Tanahashi,Masayuki; Niwa,Hiroshi; Funai,Kazuhito; Kohno,Takashi; Suda,Takafumi; Sugimura,Haruhiko

doi:10.3892/or.2013.2630

CD74-ROS1 fusion transcripts in resected non-small cell lung carcinoma

Authors:
- Shun Matsuura
- Kazuya Shinmura
- Takaharu Kamo
- Hisaki Igarashi
- Kyoko Maruyama
- Mari Tajima
- Hiroshi Ogawa
- Masayuki Tanahashi
- Hiroshi Niwa
- Kazuhito Funai
- Takashi Kohno
- Takafumi Suda
- Haruhiko Sugimura
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Affiliations: Department of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka 431-3192, Japan, Division of Pathology, Respiratory Disease Center, Seirei Mikatahara General Hospital, Hamamatsu, Shizuoka 433-8558, Japan, Division of Thoracic Surgery, Respiratory Disease Center, Seirei Mikatahara General Hospital, Hamamatsu, Shizuoka 433-8558, Japan, Department of Surgery 1, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka 431-3192, Japan, Division of Genome Biology, National Cancer Center Research Institute, Chuo-ku, Tokyo 104-0045, Japan, Department of Internal Medicine 2, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka 431-3192, Japan
Published online on: July 19, 2013 https://doi.org/10.3892/or.2013.2630
Pages: 1675-1680

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Abstract

The recent discovery of fusion oncokinases in a subset of non-small cell lung carcinomas (NSCLCs) is of considerable clinical interest, since NSCLCs that express such fusion oncokinases are reportedly sensitive to kinase inhibitors. To better understand the role of recently identified ROS1 and RET fusion oncokinases in pulmonary carcinogenesis, we examined 114 NSCLCs for SLC34A2-ROS1, EZR-ROS1, CD74-ROS1 and KIF5B-RET fusion transcripts using RT-polymerase chain reaction and subsequent sequencing analyses. Although the expression of SLC34A2-ROS1, EZR-ROS1, or KIF5B-RET fusion transcripts was not detected in any of the cases, the expression of CD74-ROS1 fusion transcripts was detected in one (0.9%) of the 114 NSCLCs. The fusion occurred between exon 6 of CD74 and exon 34 of ROS1 and was an in-frame alteration. The mutation was detected in a woman without a history of smoking. Histologically, the carcinoma was an adenocarcinoma with a predominant acinar pattern; notably, a mucinous cribriform pattern and a solid signet-ring cell pattern were also observed in part of the adenocarcinoma. ROS1 protein overexpression was immunohistochemically detected in a cancer-specific manner in both the primary cancer and the lymph node metastatic cancer. No somatic mutations were detected in the mutation cluster regions of the KRAS, EGFR, BRAF and PIK3CA genes and the entire coding region of p53 in the carcinoma, and the expression of ALK fusion was negative. The above results suggest that CD74-ROS1 fusion is involved in the carcinogenesis of a subset of NSCLCs and may contribute to the elucidation of the characteristics of ROS1 fusion-positive NSCLC in the future.

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1	Soda M, Choi YL, Enomoto M, Takada S, Yamashita Y, Ishikawa S, Fujiwara S, Watanabe H, Kurashina K, Hatanaka H, Bando M, Ohno S, Ishikawa Y, Aburatani H, Niki T, Sohara Y, Sugiyama Y and Mano H: Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature. 448:561–566. 2007. View Article : Google Scholar : PubMed/NCBI
2	Shinmura K, Kageyama S, Tao H, Bunai T, Suzuki M, Kamo T, Takamochi K, Suzuki K, Tanahashi M, Niwa H, Ogawa H and Sugimura H: EML4-ALK fusion transcripts, but no NPM-, TPM3-, CLTC-, ATIC-, or TFG-ALK fusion transcripts, in non-small cell lung carcinomas. Lung Cancer. 61:163–169. 2008. View Article : Google Scholar : PubMed/NCBI
3	Shinmura K, Kageyama S, Igarashi H, Kamo T, Mochizuki T, Suzuki K, Tanahashi M, Niwa H, Ogawa H and Sugimura H: EML4-ALK fusion transcripts in immunohistochemically ALK-positive non-small cell lung carcinomas. Exp Ther Med. 1:271–275. 2010. View Article : Google Scholar : PubMed/NCBI
4	Takeuchi K, Soda M, Togashi Y, Suzuki R, Sakata S, Hatano S, Asaka R, Hamanaka W, Ninomiya H, Uehara H, Lim Choi Y, Satoh Y, Okumura S, Nakagawa K, Mano H and Ishikawa Y: RET, ROS1 and ALK fusions in lung cancer. Nat Med. 18:378–381. 2012. View Article : Google Scholar : PubMed/NCBI
5	Lipson D, Capelletti M, Yelensky R, Otto G, Parker A, Jarosz M, Curran JA, Balasubramanian S, Bloom T, Brennan KW, Donahue A, Downing SR, Frampton GM, Garcia L, Juhn F, Mitchell KC, White E, White J, Zwirko Z, Peretz T, Nechushtan H, Soussan-Gutman L, Kim J, Sasaki H, Kim HR, Park SI, Ercan D, Sheehan CE, Ross JS, Cronin MT, Jänne PA and Stephens PJ: Identification of new ALK and RET gene fusions from colorectal and lung cancer biopsies. Nat Med. 18:382–384. 2012. View Article : Google Scholar : PubMed/NCBI
6	Casaluce F, Sgambato A, Maione P, Rossi A, Ferrara C, Napolitano A, Palazzolo G, Ciardiello F and Gridelli C: ALK inhibitors: a new targeted therapy in the treatment of advanced NSCLC. Target Oncol. 8:55–67. 2013. View Article : Google Scholar : PubMed/NCBI
7	Shaw AT and Solomon B: Targeting anaplastic lymphoma kinase in lung cancer. Clin Cancer Res. 17:2081–2086. 2011. View Article : Google Scholar : PubMed/NCBI
8	O’Bryant CL, Wenger SD, Kim M and Thompson LA: Crizotinib: a new treatment option for ALK-positive non-small cell lung cancer. Ann Pharmacother. 47:189–197. 2013.PubMed/NCBI
9	Rikova K, Guo A, Zeng Q, Possemato A, Yu J, Haack H, Nardone J, Lee K, Reeves C, Li Y, Hu Y, Tan Z, Stokes M, Sullivan L, Mitchell J, Wetzel R, Macneill J, Ren JM, Yuan J, Bakalarski CE, Villen J, Kornhauser JM, Smith B, Li D, Zhou X, Gygi SP, Gu TL, Polakiewicz RD, Rush J and Comb MJ: Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer. Cell. 131:1190–1203. 2007. View Article : Google Scholar : PubMed/NCBI
10	Li C, Fang R, Sun Y, Han X, Li F, Gao B, Iafrate AJ, Liu XY, Pao W, Chen H and Ji H: Spectrum of oncogenic driver mutations in lung adenocarcinomas from East Asian never smokers. PLoS One. 6:e282042011. View Article : Google Scholar : PubMed/NCBI
11	Kohno T, Ichikawa H, Totoki Y, Yasuda K, Hiramoto M, Nammo T, Sakamoto H, Tsuta K, Furuta K, Shimada Y, Iwakawa R, Ogiwara H, Oike T, Enari M, Schetter AJ, Okayama H, Haugen A, Skaug V, Chiku S, Yamanaka I, Arai Y, Watanabe S, Sekine I, Ogawa S, Harris CC, Tsuda H, Yoshida T, Yokota J and Shibata T: KIF5B-RET fusions in lung adenocarcinoma. Nat Med. 18:375–377. 2012. View Article : Google Scholar : PubMed/NCBI
12	Bergethon K, Shaw AT, Ou SH, Katayama R, Lovly CM, McDonald NT, Massion PP, Siwak-Tapp C, Gonzalez A, Fang R, Mark EJ, Batten JM, Chen H, Wilner KD, Kwak EL, Clark JW, Carbone DP, Ji H, Engelman JA, Mino-Kenudson M, Pao W and Iafrate AJ: ROS1 rearrangements define a unique molecular class of lung cancers. J Clin Oncol. 30:863–870. 2012. View Article : Google Scholar : PubMed/NCBI
13	Seo JS, Ju YS, Lee WC, Shin JY, Lee JK, Bleazard T, Lee J, Jung YJ, Kim JO, Shin JY, Yu SB, Kim J, Lee ER, Kang CH, Park IK, Rhee H, Lee SH, Kim JI, Kang JH and Kim YT: The transcriptional landscape and mutational profile of lung adenocarcinoma. Genome Res. 22:2109–2119. 2012. View Article : Google Scholar : PubMed/NCBI
14	Davies KD, Le AT, Theodoro MF, Skokan MC, Aisner DL, Berge EM, Terracciano LM, Cappuzzo F, Incarbone M, Roncalli M, Alloisio M, Santoro A, Camidge DR, Varella-Garcia M and Doebele RC: Identifying and targeting ROS1 gene fusions in non-small cell lung cancer. Clin Cancer Res. 18:4570–4579. 2012. View Article : Google Scholar : PubMed/NCBI
15	Rimkunas VM, Crosby KE, Li D, Hu Y, Kelly ME, Gu TL, Mack JS, Silver MR, Zhou X and Haack H: Analysis of receptor tyrosine kinase ROS1-positive tumors in non-small cell lung cancer: identification of a FIG-ROS1 fusion. Clin Cancer Res. 18:4449–4457. 2012. View Article : Google Scholar : PubMed/NCBI
16	Yokota K, Sasaki H, Okuda K, Shimizu S, Shitara M, Hikosaka Y, Moriyama S, Yano M and Fujii Y: KIF5B/RET fusion gene in surgically-treated adenocarcinoma of the lung. Oncol Rep. 28:1187–1192. 2012.
17	Yoshida A, Kohno T, Tsuta K, Wakai S, Arai Y, Shimada Y, Asamura H, Furuta K, Shibata T and Tsuda H: ROS1-rearranged lung cancer: a clinicopathologic and molecular study of 15 surgical sases. Am J Surg Pathol. 37:554–562. 2013. View Article : Google Scholar : PubMed/NCBI
18	Schmid K, Oehl N, Wrba F, Pirker R, Pirker C and Filipits M: EGFR/KRAS/BRAF mutations in primary lung adenocarcinomas and corresponding locoregional lymph node metastases. Clin Cancer Res. 15:4554–4560. 2009. View Article : Google Scholar : PubMed/NCBI
19	Pao W and Girard N: New driver mutations in non-small-cell lung cancer. Lancet Oncol. 12:175–180. 2011. View Article : Google Scholar : PubMed/NCBI
20	Ulivi P, Romagnoli M, Chiadini E, Casoni GL, Capelli L, Gurioli C, Zoli W, Saragoni L, Dubini A, Tesei A, Amadori D and Poletti V: Assessment of EGFR and K-ras mutations in fixed and fresh specimens from transesophageal ultrasound-guided fine needle aspiration in non-small cell lung cancer patients. Int J Oncol. 41:147–152. 2012.
21	Thomas M, Kalita A, Labrecque S, Pim D, Banks L and Matlashewski G: Two polymorphic variants of wild-type p53 differ biochemically and biologically. Mol Cell Biol. 19:1092–1100. 1999.PubMed/NCBI
22	Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar
23	Rodig SJ, Mino-Kenudson M, Dacic S, Yeap BY, Shaw A, Barletta JA, Stubbs H, Law K, Lindeman N, Mark E, Janne PA, Lynch T, Johnson BE, Iafrate AJ and Chirieac LR: Unique clinicopathologic features characterize ALK-rearranged lung adenocarcinoma in the western population. Clin Cancer Res. 15:5216–5223. 2009. View Article : Google Scholar : PubMed/NCBI
24	Jokoji R, Yamasaki T, Minami S, Komuta K, Sakamaki Y, Takeuchi K and Tsujimoto M: Combination of morphological feature analysis and immunohistochemistry is useful for screening of EML4-ALK-positive lung adenocarcinoma. J Clin Pathol. 63:1066–1070. 2010. View Article : Google Scholar : PubMed/NCBI