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Mutations of the BRAF gene in squamous cell carcinoma of the head and neck

Abstract

The RAF/MEK/ERK (MAPK) signal transduction cascade is an important mediator of a number of cellular fates including growth, proliferation and survival. The BRAF gene, one of the human isoforms of RAF, is activated by oncogenic RAS, leading to cooperative effects in cells responding to growth factor signals. This study was performed to elucidate a possible function of BRAF in squamous cell carcinoma of the head and neck (HNSCC). Mutations of BRAF and KRAS2 were evaluated in 89 HNSCC and corresponding normal mucosa by direct DNA sequencing analyses after microdissection. The results obtained were correlated with histopathological variables. Activating BRAF missense mutations were identified in 3/89 HNSCC (3%). KRAS2 mutations were found in five out of 89 (6%) HNSCC examined. There were no mutations of KRAS2 and BRAF in non-neoplastic mucosa. We failed to observe a correlation between BRAF or KRAS2 mutations and histopathological factors. Our data indicate that BRAF gene mutations are relatively rare events in HNSCC. Although uncommon, BRAF mutations may identify a subset of patients with HNSCC sensitive to targeted therapy.

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Abbreviations

HNSCC:

head and neck squamous cell carcinoma

MAP:

mitogen-activated protein

ERK:

extracellular signal-regulated kinase

References

  • Brose MS, Volpe P, Feldman M, Kumar M, Rishi I, Gerrero R, Einhorn E, Herlyn MJ, Nicholson A, Roth JA, Albelda SM, Davies H, Cox C, Brignell G, Stephens P, Futreal PA, Wooster R, Stratton MR and Weber BL . (2002). Cancer Res., 62, 6997–7000.

  • Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, Teague J, Woffendin H, Garnett MJ, Bottomley W, Davis N, Dicks E, Ewing R, Floyd Y, Gray K, Hall SR, Hughes J, Kosmidou V, Menzies A, Mould C, Parker A, Stevens C, Watt S, Hooper S, Wilson R, Jayatilake H, Gusterson BA, Cooper C, Shipley J, Hargrave D, Pritchard-Jones K, Maitland N, Chenevix-Trench G, Riggins GJ, Bigner DDG, Cossu A, Flanagan A, Nicholson A, Ho JW, Leung SY, Yuen ST, Weber BL, Seigler HF, Darrow TL, Paterson H, Marais R, Marshall CJ, Wooster R, Stratton MR and Futreal PA . (2002). Nature, 417, 949–954.

  • Fitzgerald K, Harrington A and Leder P . (2000). Oncogene, 19, 4191–4198.

  • Garcia J, de Gunzburg J, Eychene A, Gisselbrecht S and Porteu F . (2001). Mol. Cell. Biol., 21, 2659–2670.

  • Gire V and Wynford-Thomas D . (2000). Oncogene, 19, 737–744.

  • Hagemann C and Rapp UR . (1999). Exp. Cell Res., 253, 34–46.

  • Hakimi MA, Bochar DA, Chenoweth J, Lane WS, Mandel G and Shiekhattar R . (2002). Proc. Natl. Acad. Sci. USA, 99, 7420–7425.

  • Hao D and Rowinsky EK . (2002). Cancer Invest., 20, 387–404.

  • Hoa M, Davis SL, Ames SJ and Spanjaard RA . (2002). Cancer Res., 62, 7154–7156.

  • Leder A, Lebel M, Zhou F, Fontaine K, Bishop A and Leder P . (2002). Oncogene, 21, 6657–6668.

  • Liao Y, Satoh T, Gao X, Jin TG, Hu CD and Kataoka T . (2001). J. Biol. Chem., 276, 28478–28483.

  • Mikula M, Schreiber M, Husak Z, Kucerova L, Ruth J, Wieser R, Zatloukal K, Beug H, Wagner EF and Baccarini M . (2001). EMBO J., 20, 1952–1962.

  • Naoki K, Chen TH, Richards WG, Sugarbaker DJ and Meyerson M . (2002). Cancer Res., 62, 7001–7003.

  • Peyssonnaux C and Eychene A . (2001). Biol. Cell., 93, 53–62.

  • Pindborg JJ, Reichart PA, Smith CJ and van der Waal I (eds). (1997). Histological Typing of Cancer and Precancer of the Oral Mucosa. Springer: Berlin, Heidelberg, New York.

    Book  Google Scholar 

  • Pollock PM, Harper UL, Hansen KS, Yudt LM, Stark M, Robbins CM, Moses TY, Hostetter G, Wagner U, Kakareka J, Salem G, Pohida T, Heenan P, Duray P, Kallioniemi O, Hayward NK, Trent JM and Meltzer PS . (2003). Nat. Genet., 33, 19–20.

  • Rajagopalan H, Bardelli A, Lengauer C, Kinzler KW, Vogelstein B and Velculescu VE . (2002). Nature, 418, 934.

  • Shanmugaratnam K. (ed). (1991). Histological Typing of Tumors of the Upper Respiratoty Tract and Ear. Springer: Berlin, Heidelberg, New York.

    Book  Google Scholar 

  • Sobin LH and Wittekind CH . (2002). UICC: TNM Classification of Malignant Tumors, 6th ed Wiley-Liss: New York.

    Google Scholar 

  • Tannapfel A, Benicke M, Katalinic A, Uhlmann D, Kockerling F, Hauss J and Wittekind C . (2000). Gut, 47, 721–727.

  • Tannapfel A, Busse C, Weinans L, Benicke M, Katalinic A, Geissler F, Hauss J and Wittekind C . (2001). Oncogene, 20, 7104–7109.

  • Tannapfel A and Weber A . (2001). Eur. Arch. Otorhinolaryngol., 258, 83–88.

  • Weber CK, Slupsky JR, Kalmes HA and Rapp UR . (2001). Cancer Res., 61, 3595–3598.

  • Xu J, Gimenez-Conti IB, Cunningham JE, Collet AM, Luna MA, Lanfranchi HE, Spitz MR and Conti CJ . (1998). Cancer, 83, 204–212.

  • Yuen ST, Davies H, Chan TL, Ho JW, Bignell GR, Cox C, Stephens P, Edkins S, Tsui WW, Chan AS, Futreal PA, Stratton MR, Wooster R and Leung SY . (2002). Cancer Res., 62, 6451–6455.

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Acknowledgements

This paper was supported by the Bundesministerium für Bildung und Forschung (BMB+F), Interdisciplinary Centre for Clinical Research (IZKF) at the University of Leipzig (01KS9504/1, Project D01).

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Correspondence to Andrea Tannapfel.

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Weber, A., Langhanki, L., Sommerer, F. et al. Mutations of the BRAF gene in squamous cell carcinoma of the head and neck. Oncogene 22, 4757–4759 (2003). https://doi.org/10.1038/sj.onc.1206705

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