J Korean Med Sci.  2013 Oct;28(10):1555-1558. 10.3346/jkms.2013.28.10.1555.

RET Fusion Genes in Korean Non-Small Cell Lung Cancer

• Yoo SS
• Jin G
• Jung HJ
• Hong MJ
• Choi JE
• Jeon HS
• Lee SY
• Lim JO
• Park JY

• KMID: 1777699
• DOI: http://doi.org/10.3346/jkms.2013.28.10.1555

Abstract

Recently, rearranged during transfection (RET) fusions have been identified in approximately 1% of non-small cell lung cancer (NSCLC). To know the prevalence of RET fusion genes in Korean NSCLCs, we examined the RET fusion genes in 156 surgically resected NSCLCs using a reverse transcriptase polymerase chain reaction. Two KIF5B-RET fusions and one CCDC6-RET fusion were identified. All three patients were females and never smokers with adenocarcinomas. RET fusion genes were mutually exclusive from EGFR, KRAS mutations and EML4-ALK fusion. RET fusion genes occur 1.9% (3 of 156) of surgically treated NSCLC patients in Koreans.

Keyword

RET Fusion; KIF5B; CCDC6; Carcinoma, Non-Small-Cell Lung; Korean

MeSH Terms

Asian Continental Ancestry Group/*genetics
Carcinoma, Non-Small-Cell Lung/epidemiology/*genetics/surgery
Cytoskeletal Proteins/genetics
Female
Humans
Kinesin/genetics
Lung Neoplasms/epidemiology/*genetics/surgery
Middle Aged
Oncogene Proteins, Fusion/*genetics
Proto-Oncogene Proteins c-ret/*genetics
Republic of Korea/epidemiology
Sequence Analysis, DNA
Cytoskeletal Proteins
Oncogene Proteins, Fusion
Proto-Oncogene Proteins c-ret
Kinesin

Figure

• 

  Fig. 1 Detection of RET fusion genes by RT-PCR and sequencing. RT-PCR results of KIF5B-RET fusion genes (A). Nucleotide sequencing of the RCR product of KIF5B-RET (K15;R12) (B). RT-PCR result of CCDC6-RET fusion gene (C). Nucleotide sequencing of the RCR product of CCDC6-RET (D).

Reference

1. Molina JR, Yang P, Cassivi SD, Schild SE, Adjei AA. Non-small cell lung cancer: epidemiology, risk factors, treatment, and survivorship. Mayo Clin Proc. 2008; 83:584–594.

2. Goffin J, Lacchetti C, Ellis PM, Ung YC, Evans WK. Lung Cancer Disease Site Group of Cancer Care Ontario's Program in Evidence-Based Care. First-line systemic chemotherapy in the treatment of advanced non-small cell lung cancer: a systematic review. J Thorac Oncol. 2010; 5:260–274.

3. Sequist LV, Martins RG, Spigel D, Grunberg SM, Spira A, Jänne PA, Joshi VA, McCollum D, Evans TL, Muzikansky A, et al. First-line gefitinib in patients with advanced non-small-cell lung cancer harboring somatic EGFR mutations. J Clin Oncol. 2008; 26:2442–2449.

4. Kwak EL, Bang YJ, Camidge DR, Shaw AT, Solomon B, Maki RG, Ou SH, Dezube BJ, Jänne PA, Costa DB, et al. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med. 2010; 363:1693–1703.

5. Takeuchi K, Soda M, Togashi Y, Suzuki R, Sakata S, Hatano S, Asaka R, Hamanaka W, Ninomiya H, Uehara H, et al. RET, ROS1 and ALK fusions in lung cancer. Nat Med. 2012; 18:378–381.

6. Lipson D, Capelletti M, Yelensky R, Otto G, Parker A, Jarosz M, Curran JA, Balasubramanian S, Bloom T, Brennan KW, et al. Identification of new ALK and RET gene fusions from colorectal and lung cancer biopsies. Nat Med. 2012; 18:382–384.

7. Wang R, Hu H, Pan Y, Li Y, Ye T, Li C, Luo X, Wang L, Li H, Zhang Y, et al. RET fusions define a unique molecular and clinicopathologic subtype of non-small-cell lung cancer. J Clin Oncol. 2012; 30:4352–4359.

8. Matsubara D, Kanai Y, Ishikawa S, Ohara S, Yoshimoto T, Sakatani T, Oguni S, Tamura T, Kataoka H, Endo S, et al. Identification of CCDC6-RET fusion in the human lung adenocarcinoma cell line, LC-2/ad. J Thorac Oncol. 2012; 7:1872–1876.

9. Kohno T, Ichikawa H, Totoki Y, Yasuda K, Hiramoto M, Nammo T, Sakamoto H, Tsuta K, Furuta K, Shimada Y, et al. KIF5B-RET fusions in lung adenocarcinoma. Nat Med. 2012; 18:375–377.

10. Eng C. RET proto-oncogene in the development of human cancer. J Clin Oncol. 1999; 17:380–393.

11. Bounacer A, Wicker R, Caillou B, Cailleux AF, Sarasin A, Schlumberger M, Suárez HG. High prevalence of activating ret proto-oncogene rearrangements, in thyroid tumors from patients who had received external radiation. Oncogene. 1997; 15:1263–1273.

12. Chao BH, Briesewitz R, Villalona-Calero MA. RET fusion genes in non-small-cell lung cancer. J Clin Oncol. 2012; 30:4439–4441.

13. Pao W, Hutchinson KE. Chipping away at the lung cancer genome. Nat Med. 2012; 18:349–351.

14. Lee SY, Kim MJ, Jin G, Yoo SS, Park JY, Choi JE, Jeon HS, Cho S, Lee EB, Cha SI, et al. Somatic mutations in epidermal growth factor receptor signaling pathway genes in non-small cell lung cancers. J Thorac Oncol. 2010; 5:1734–1740.

15. Ju YS, Lee WC, Shin JY, Lee S, Bleazard T, Won JK, Kim YT, Kim JI, Kang JH, Seo JS. A transforming KIF5B and RET gene fusion in lung adenocarcinoma revealed from whole-genome and transcriptome sequencing. Genome Res. 2012; 22:436–445.