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High Incidence of Null-Type Mutations of the TP53 Gene in Japanese Patients with Head and Neck Squamous Cell Carcinoma

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DOI: 10.4236/jct.2014.57075    2,732 Downloads   3,530 Views   Citations

ABSTRACT

Objective: Molecular targeting therapy has not been generally established in head and neck squamous cell carcinoma (HNSCC) except for cetuximab treatment for targeting epidermal growth factor receptor (EGFR). We analyzed alterations of the TP53, KRAS2, and EGFR genes in Japanese HNSCC to identify subpopulations of tumors potentially susceptible or not susceptible to specific therapy based on their genetic alterations. Materials and Methods: A total of 56 Japanese subjects were included in this study. Genomic DNA of exons 5 - 9 of the TP53, exons 1 and 2 of the KRAS2, exons 19 - 22 of the EGFR, and their flanking sequences were amplified by polymerase chain reaction (PCR) followed by direct sequencing. Splicing variants of EGFR were examined by reverse transcription (RT)-PCR. Results: Mutations of the TP53 and KRAS genes were detected in 25 (45%) and 2 (4%) of 56 HNSCC cases, respectively, while neither mutation nor splicing variant of EGFR was observed. The TP53 mutation did not correlate with clinical stages or primary sites of the tumors. The patterns of nucleotide substitutions specific to HNSCC were not observed. However, the incidence of null-type mutations of the TP53, which cannot be detected as abnormal by conventional immunohistochemical (IHC) studies, was significantly higher (10/25; 40%) than that of HNSCC reported in other countries. Conclusion: Frequent TP53 mutations, especially null-type mutations, but infrequent or no alterations of the KRAS and EGFR suggest that the sequencing analysis of theTP53 mutation rather than IHC analysis of p53 provides a potentially useful marker to predict the response of HNSCC to chemotherapy or radiotherapy.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

Ebihara, Y. , Iwai, M. , Akashi, K. , Ito, T. , Omura, G. , Saito, Y. , Yoshida, M. , Ando, M. , Asakage, T. , Yamasoba, T. and Murakami, Y. (2014) High Incidence of Null-Type Mutations of the TP53 Gene in Japanese Patients with Head and Neck Squamous Cell Carcinoma. Journal of Cancer Therapy, 5, 664-671. doi: 10.4236/jct.2014.57075.

References

[1] Vermorken, J.B., Remenar, E., van Herpen, C., Gorlia, T., Mesia, R., Degardin, M., Stewart, J.S., Jelic, S., Betka, J., Preiss, J.H., van den Weyngaert, D., Awada, A., Cupissol, D., Kienzer, H.R., Rey, A., Desaunois, I., Bernier, J. and Lefebvre, J.L. (2007) Cisplatin, Fluorouracil, and Docetaxel in Unresectable Head and Neck Cancer. The New England Journal of Medicine, 357, 1695-1704.
http://dx.doi.org/10.1056/NEJMoa071028
[2] Leemans, C.R., Braakhuis, B.J. and Brakenhoff, R.H. (2011) The Molecular Biology of Head and Neck Cancer. Nature Review Cancer, 11, 9-22. http://dx.doi.org/10.1038/nrc2982
[3] Karapetis, C.S., Khambata-Ford, S., Jonker, D.J., O’Callaghan, C.J., Tu, D., Tebbutt, N.C., Simes, R.J., Chalchal, H., Shapiro, J.D., Robitaille, S., Price, T.J., Shepherd, L., Au, H.J., Langer, C., Moore, M.J. and Zalcberg, J.R. (2008) K-ras Mutations and Benefit from Cetuximab in Advanced Colorectal Cancer. The New England Journal of Medicine, 359, 1757-1765. http://dx.doi.org/10.1056/NEJMoa0804385
[4] Montano, N., Cenci, T., Martini, M., D’Alessandris, Q.G., Pelacchi, F., Ricci-Vitiani, L., Maira, G., De Maria, R., Larocca, L.M. and Pallini, R. (2011) Expression of EGFRvIII in Glioblastoma: Prognostic Significance Revisited. Neoplasia, 13, 1113-1121.
[5] Temam, S., Flahault, A., Périé, S., Monceaux, G., Coulet, F., Callard, P., Bernaudin, J.F., St Guily, J.L. and Fouret, P. (2000) p53 Gene Status as a Predictor of Tumor Response to Induction Chemotherapy of Patients with Locoregionally Advanced Squamous Cell Carcinomas of the Head and Neck. Journal of Clinical Oncology, 18, 385-394.
[6] Cabelguenne, A., Blons, H., de Waziers, I., Carnot, F., Houllier, A.M., Soussi, T., Brasnu, D., Beaune, P., Laccourreye, O. and Laurent-Puig, P. (2000) p53 Alterations Predict Tumor Response to Neoadjuvant Chemotherapy in Head and Neck Squamous Cell Carcinoma: A Prospective Series. Journal of Clinical Oncology, 18, 1465-1473.
[7] Perrone, F., Bossi, P., Cortelazzi, B., Locati, L., Quattrone, P., Pierotti, M., Pilotti, S. and Licitra, L. (2010) TP53 Mutations and Pathologic Complete Response to Neoadjuvant Cisplatin and Fluorouracil Chemotherapy in Resected Oral Cavity Squamous Cell Carcinoma. Journal of Clinical Oncology, 28, 761-766. http://dx.doi.org/10.1200/JCO.2009.22.4170
[8] Koch, W.M., Brennan, J.A., Zahurak, M., Goodman, S.N., Westra, W.H., Schwab, D., Yoo, G.H., Lee, D.J., Forastiere, A.A. and Sidransky, D. (1996) p53 Mutation and Locoregional Treatment Failure in Head and Neck Squamous Cell Carcinoma. Journal of the National Cancer Institute, 88, 1580-1586. http://dx.doi.org/10.1093/jnci/88.21.1580
[9] Alsner, J., S?rensen, S.B. and Overgaard, J. (2001) TP53 Mutation Is Related to Poor Prognosis after Radiotherapy, but Not Surgery, in Squamous Cell Carcinoma of the Head and Neck. Radiotherapy and Oncology, 59, 179-185. http://dx.doi.org/10.1016/S0167-8140(01)00301-2
[10] Eriksen, J.G., Alsner, J., Steiniche, T. and Overgaard, J. (2005) The Possible Role of TP53 Mutation Status in the Treatment of Squamous Cell Carcinomas of the Head and Neck (HNSCC) with Radiotherapy with Different Overall Treatment Times. Radiotherapy and Oncology, 76, 135-142.
http://dx.doi.org/10.1016/j.radonc.2005.05.004
[11] Erber, R., Conradt, C., Homann, N., Enders, C., Finckh, M., Dietz, A., Weidauer, H. and Bosch, F.X. (1998) TP53 DNA Contact Mutations Are Selectively Associated with Allelic Loss and Have a Strong Clinical Impact in Head and Neck Cancer. Oncogene, 16, 1671-1679.
http://dx.doi.org/10.1038/sj.onc.1201690
[12] Poeta, M.L., Manola, J., Goldwasser, M.A., Forastiere, A., Benoit, N., Califano, J.A., Ridge, J.A., Goodwin, J., Kenady, D., Saunders, J., Westra, W., Sidransky, D. and Koch, W.M. (2007) TP53 Mutations and Survival in Squamous-Cell Carcinoma of the Head and Neck. The New England Journal of Medicine, 357, 2552-2561. http://dx.doi.org/10.1056/NEJMoa073770
[13] Bodner, S.M., Minna, J.D., Jensen, S.M., D’Amico, D., Carbone, D., Mitsudomi, T., Fedorko, J., Buchhagen, D.L., Nau, M.M. and Gazdar, A.F. (1992) Expression of Mutant p53 Proteins in Lung Cancer Correlates with the Class of p53 Gene Mutation. Oncogene, 7, 743-749.
[14] Hashimoto, T., Tokuchi, Y., Hayashi, M., Kobayashi, Y., Nishida, K., Hayashi, S., Ishikawa, Y., Tsuchiya, S., Nakagawa, K., Hayashi, J. and Tsuchiya, E. (1999) p53 Null Mutations Undetected by Immunohistochemical Staining Predict a Poor Outcome with Early-Stage Non-Small Cell Lung Carcinomas. Cancer Research, 59, 5572-5577.
[15] Mroz, E.A. and Rocco, J.W. (2010) Functional p53 Status as a Biomarker for Chemotherapy Response in Oral-Cavity Cancer. Journal of Clinical Oncology, 28, 715-717.
http://dx.doi.org/10.1200/JCO.2009.26.3475
[16] Kikuchi, S., Iwai, M., Sakurai-Yageta, M., Tsuboi, Y., Ito, T., Masuda, T., Tsuda, H., Kanai, Y., Onizuka, M., Sato, Y. and Murakami, Y. (2012) Expression of a Splicing Variant of the CADM1 Specific to Small Cell Lung Cancer. Cancer Science, 103, 1051-1057.
http://dx.doi.org/10.1111/j.1349-7006.2012.02277.x
[17] Fujii, S., Uryu, H., Akashi, K., Suzuki, K., Yamazak, M., Tahara, M., Hayashi, R. and Ochiai, A. (2013) Clinical Significance of KRAS Gene Mutation and Epidermal Growth Factor Receptor Expression in Japanese Patients with Squamous Cell Carcinoma of the Larynx, Oropharynx and Hypopharynx. International Journal of Clinical Oncology, 18, 454-463. http://dx.doi.org/10.1007/s10147-012-0402-z
[18] Bissada, E., Abboud, O., Abou, C.Z., Guertin, L., Weng, X., Nguyen-Tan, P.F., Tabet, J.C., Thibaudeau, E., Lambert, L., Audet, M.L., Fortin, B. and Soulieres, D. (2013) Prevalence of K-RAS Codons 12 and 13 Mutations in Locally Advanced Head and Neck Squamous Cell Carcinoma and Impact on Clinical Outcomes. International Journal of Otolaryngology, 2013, Article ID: 848021.
http://dx.doi.org/10.1155/2013/848021
[19] De Carvalho, T.G., De Carvalho, A.C., Maia, D.C., Ogawa, J.K., Carvalho, A.L. and Vettore, A.L. (2013) Search for Mutations in Signaling Pathways in Head and Neck Squamous Cell Carcinoma. Oncology Reports, 30, 334-340.
[20] Wikstrand, C.J., Hale, L.P., Batra, S.K., Hill, M.L., Humphrey, P.A., Kurpad, S.N., McLendon, R.E., Moscatello, D., Pegram, C.N., Reist, C.J., Traweek, S.T., Wong, A.J., Zalutsky, M.R. and Bigner, D.D. (1995) Monoclonal Antibodies against EGFRvIII Are Tumor Specific and React with Breast and Lung Carcinomas and Malignant Gliomas. Cancer Research, 55, 3140-3148.
[21] Olshan, A.F., Weissler, M.C., Pei, H. and Conway, K. (1997) p53 Mutations in Head and Neck Cancer: New Data and Evaluation of Mutational Spectra. Cancer Epidemiology Biomarkers and Prevention, 6, 499-504.
[22] (2009) International Agency for Research on Cancer TP53 Database R14 Release. http://www-p53.iarc.fr/

  
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