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Frequent Copy Gain of the MET Gene in Hypopharyngeal and Laryngeal Cancer in the Japanese Population

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DOI: 10.4236/jct.2015.612119    2,008 Downloads   2,417 Views  

ABSTRACT

Molecular targeting therapy to specific genetic alterations has not been established in head and neck squamous cell carcinoma (HNSCC) except for cetuximab treatment. To characterize alterations of actionable oncogenes in HNSCC, we examined the gain of copy and mutation of the MET gene in 54 Japanese HNSCC. Copy gain of the MET was analyzed by droplet digital PCR (ddPCR) and quantitative real time PCR (qPCR) using 2 distinct fragments of the gene, and mutation was examined in exons 14 - 19 of MET by Sanger sequencing. Both ddPCR and qPCR showed significantly correlated results in copy number at two distinct fragments of the MET gene (R = 0.96 and R = 0.78), although ddPCR gave more significant and sensitive results. Copy gain of the MET was detected in 10 of 54 (19%) HNSCCs and more frequently observed in tumors of the hypopharynx (4 of 12; 33%) or larynx (5 of 13; 38%) than those of the oral cavity (1 of 21; 4%) or oropharynx (0 of 8; 0%), suggesting the existence of site-specific features in the oncogenic mechanisms of HNSCCs. Copy gain of the MET was also observed preferentially in older patients, although no correlation in other parameters, including clinical stages and overall or recurrence-free survival, was observed. On the other hand, of the two HNSCCs in which nucleotide substitution was detected, one was R1040Q in exon 15 with unknown function, and the other was a silent mutation in exon16. These results suggest that copy gain of the MET can provide an indicator for treatment with tyrosine kinase inhibitors for MET in a subset of hypopharyngeal or laryngeal cancer.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

Akashi, K. , Ebihara, Y. , Omura, G. , Saito, Y. , Yoshida, M. , Ando, M. , Asakage, T. , Yamasoba, T. and Murakami, Y. (2015) Frequent Copy Gain of the MET Gene in Hypopharyngeal and Laryngeal Cancer in the Japanese Population. Journal of Cancer Therapy, 6, 1093-1102. doi: 10.4236/jct.2015.612119.

References

[1] Jemal, A., Thun, M.J., Ries, L.G., Howe, H.L., Weir, H.K., Center, M.M., et al. (2008) Annual Report to the Nation on the Status of Cancer, 1975-2005, Featuring Trends in Lung Cancer, Tobacco Use, and Tobacco Control. Journal of the National Cancer Institute, 100, 1672-1694.
http://dx.doi.org/10.1093/jnci/djn389
[2] Carvalho, A.L., Nishimoto, I.N., Califano, J.A. and Kowalski, L.P. (2005) Trends in Incidence and Prognosis for Head and Neck Cancer in the United States: A Site-Specific Analysis of the SEER Database. International Journal of Cancer, 114, 806-816.
http://dx.doi.org/10.1002/ijc.20740
[3] Bonner, J.A., Harari, P.M., Giralt, J., Azarnia, N., Shin, D.M., Cohen, R.B., et al. (2006) Radiotherapy plus Cetuximab for Squamous-Cell Carcinoma of the Head and Neck. The New England Journal of Medicine, 354, 567-578
http://dx.doi.org/10.1056/NEJMoa053422
[4] Vermorken, J.B., Mesia, R., Rivera, F., Remenar, E., Kawecki, A., Rottey, S., et al. (2008) Platinum-Based Chemotherapy plus Cetuximab in Head and Neck Cancer. The New England Journal of Medicine, 359, 1116-1127.
http://dx.doi.org/10.1056/NEJMoa0802656
[5] Park, M., Dean, M., Kaul, K., Braun, M.J., Gonda, M.A. and Vande Woude, G.F. (1987) Sequence of MET Protooncogene cDNA Has Features Characteristic of the Tyrosine Kinase Family of Growth-Factor Receptors. Proceedings of the National Academy of Sciences of the United States of America, 84, 6379-6383.
http://dx.doi.org/10.1073/pnas.84.18.6379
[6] Bottaro, D.P., Rubin, J.S., Faletto, D.L., Chan, A.M., Kmiecik, T.E., Vande Woude, G.F. and Aaronson, S.A. (1991) Identification of the Hepatocyte Growth Factor Receptor as the c-Met Proto-Oncogene Product. Science, 251, 802-804.
http://dx.doi.org/10.1126/science.1846706
[7] Peruzzi, B. and Bottaro, D.P. (2006) Targeting the c-Met Signaling Pathway in Cancer. Clinical Cancer Research, 12, 3657-3660.
http://dx.doi.org/10.1158/1078-0432.CCR-06-0818
[8] Gherardi, E., Birchmeier, W., Birchmeier, C. and Vande Woude, G.F. (2012) Targeting MET in Cancer: Rationale and Progress. Nature Reviews Cancer, 12, 89-103.
http://dx.doi.org/10.1038/nrc3205
[9] Schmidt, L., Duh, F.M., Chen, F., Kishida, T., Glenn, G., Choyke, P., et al. (1997) Germline and Somatic Mutations in the Tyrosine Kinase Domain of the MET Proto-Oncogene in Papillary Renal Carcinomas. Nature Genetics, 16, 68-73.
http://dx.doi.org/10.1038/ng0597-68
[10] Park, W.S., Dong, S.M., Kim, S.Y., Na, E.Y., Shin, M.S., Pi, J.H., et al. (1999) Somatic Mutations in the Kinase Domain of the Met/Hepatocyte Growth Factor Receptor Gene in Childhood Hepatocellular Carcinomas. Cancer Research, 59, 307-310.
[11] Nakajima, M., Sawada, H., Yamada, Y., Watanabe, A., Tatsumi, M., Yamashita, J., et al. (1999) The Prognostic Significance of Amplification and Overexpression of c-met and c-erb B-2 in Human Gastric Carcinomas. Cancer, 85, 1894-1902.
http://dx.doi.org/10.1002/(SICI)1097-0142(19990501)85:9<1894::AID-CNCR3>3.0.CO;2-J
[12] Umeki, K., Shiota, G. and Kawasaki, H. (1999) Clinical Significance of c-met Oncogene Alterations in Human Colorectal Cancer. Oncology, 56, 314-321.
http://dx.doi.org/10.1159/000011985
[13] Jardim, D.L.F., Tang, C., Gagliato, D.D.M., Falchook, G.S., Hess, K., Janku, F., et al (2014) Analysis of 1,115 Patients Tested for MET Amplification and Therapy Response in the MD Anderson Phase I Clinic. Clinical Cancer Research, 20, 6336-6345.
http://dx.doi.org/10.1158/1078-0432.CCR-14-1293
[14] Engelman, J.A., Zejnullahu, K., Mitsudomi, T., Song, Y., Hyland, C., Park, J.O., et al. (2007) MET Amplification Leads to Gefitinib Resistance in Lung Cancer by Activating ERBB3 Signaling. Science, 316, 1039-1043.
http://dx.doi.org/10.1126/science.1141478
[15] Cepero, V., Sierra, J.R., Corso, S., Ghiso, E., Casorzo, L., Perera, T., et al. (2010) MET and KRAS Gene Amplification Mediates Acquired Resistance to MET Tyrosine Kinase Inhibitors. Cancer Research, 70, 7580-7590.
http://dx.doi.org/10.1158/0008-5472.CAN-10-0436
[16] Bowers, D.C., Fan, S., Walter, K.A., Abounader, R., Williams, J.A., Rosen, E.M. and Laterra, J. (2000) Scatter Factor/Hepatocyte Growth Factor Protects against Cytotoxic Death in Human Glioblastoma via Phosphatidylinositol 3-Kinase- and AKT-Dependent Pathways. Cancer Research, 60, 4277-4283.
[17] De Bacco, F., Luraghi, P., Medico, E., Reato, G., Girolami, F., Perera, T., et al. (2011) Induction of MET by Ionizing Radiation and Its Role in Radioresistance and Invasive Growth of Cancer. Journal of the National Cancer Institute, 103, 645-661.
http://dx.doi.org/10.1093/jnci/djr093
[18] Blumenschein, G.R., Mills, G.B. and Gonzalez-Angulo, A.M. (2012) Targeting the Hepatocyte Growth Factor-cMET Axis in Cancer Therapy. Journal of Clinical Oncology, 30, 3287-3296.
http://dx.doi.org/10.1200/JCO.2011.40.3774
[19] Seiwert, T.Y., Jagadeeswaran, R., Faoro, L., Janamanchi, V., Nallasura, V., Dinali, M.E., et al. (2009)The MET Receptor Tyrosine Kinase Is a Potential Novel Therapeutic Target for Head and Neck Squamous Cell Carcinoma. Cancer Research, 69, 3021-3031.
http://dx.doi.org/10.1158/0008-5472.CAN-08-2881
[20] Christensen, J.G., Burrows, J. and Salgia, R. (2005) c-Met as a Target for Human Cancer and Characterization of Inhibitors for Therapeutic Intervention. Cancer Letters, 225, 1-26.
http://dx.doi.org/10.1016/j.canlet.2004.09.044
[21] Kim, C.H., Kim, C.H., Moon, S.K., Bae, J.H., Lee, J.H., Han, J.H., Kim, K. and Choi, E.C. (2006) Expression of Hepatocyte Growth Factor and c-met in Hypopharyngeal Squamous Cell Carcinoma. Acta Oto-Laryngologica, 126, 88-94.
http://dx.doi.org/10.1080/00016480510037014
[22] Murai, M., Shen, X., Huang, L., Carpenter, W.M., Lin, C.S. and Silverman, S. (2004) Overexpression of c-met in Oral SCC Promotes Hepatocyte Growth Factor-Induced Disruption of Cadherin Junctions and Invasion. International Journal of Oncology, 25, 831-840.
[23] Di Renzo, M.F., Olivero, M., Martone, T., Maffe, A., Maggiora, P., Stefani, A.D., et al. (2000) Somatic Mutations of the MET Oncogene Are Selected during Metastatic Spread of Human HNSC Carcinomas. Oncogene, 19, 1547-1555.
http://dx.doi.org/10.1038/sj.onc.1203455
[24] Ando, M., Saito, Y., Morikawa, T., Omura, G., Kobayashi, K., Akashi, K., et al. (2015) Maxillary Carcinosarcoma: Identification of a Novel MET Mutation in both Carcinomatous and Sarcomatous Components through Next Generation Sequencing. Head & Neck, 37, E179-E185.
http://dx.doi.org/10.1002/hed.24043
[25] Gevensleben, H., Garcia-Murillas, I., Graeser, M.K., Schiavon, G., Osin, P., Parton, M., Smith, I.E., Ashworth, A. and Turner, N.C. (2013) Noninvasive Detection of HER2 Amplification with Plasma DNA Digital PCR. Clinical Cancer Research, 19, 3276-3284.
http://dx.doi.org/10.1158/1078-0432.CCR-12-3768
[26] Chung, C.H., Parker, J.S., Karaca, G., Wu, J., Funkhouser, W.K., Moore, D., et al. (2004) Molecular Classification of Head and Neck Squamous Cell Carcinomas Using Patterns of Gene Expression. Cancer Cell, 5, 489-500.
http://dx.doi.org/10.1016/S1535-6108(04)00112-6
[27] Cappuzzo, F., Janne, P.A., Skokan, M., Finocchiaro, G., Rossi, E., Ligorio, C., et al. (2009) MET Increased Gene Copy Number and Primary Resistance to Gefitinib Therapy in Non-Small-Cell Lung Cancer Patients. Annals of Oncology, 20, 298-304.
http://dx.doi.org/10.1093/annonc/mdn635

  
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