NRAS and BRAF mutation frequency in primary oral mucosal melanoma

Buery, R.R.; Siar, C.H.; Katase, N.; Gunduz, M.; Lefeuvre, M.; Fujii, M.; Inoue, M.; Setsu, K.; Nagatsuka, H. (2011) NRAS and BRAF mutation frequency in primary oral mucosal melanoma. Oncology Reports, 26 (4). pp. 783-787. ISSN 1021-335X

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    Abstract

    Oral mucosal melanoma (OMM) is a fatal sarcoma of unknown etiology. Histological morphology and genetic events are distinct from those of its cutaneous counterpart. Mutation and up-regulation of c-kit has been identified in OMM which may activate downstream molecules such as RAS and RAF. These molecules are involved in the mitogen-activated protein kinase (MAPK) pathway leading to tremendous cell proliferation and survival. NRAS and BRAF mutation and protein expression have been studied in other melanoma subtypes. The purpose of this study was to determine RAS protein expression and NRAS and BRAF mutation in 18 primary OMM cases using immunohistochemistry and mutation analysis. Results showed that RAS is intensely expressed in both in situ and invasive OMMs. However, NRAS mutation was only observed in 2/15 polymerase chain reaction (PCR) amplified cases both of which were silent mutations. On the other hand, BRAF missense mutations were observed only in 1/15 cases with PCR amplification. NRAS and BRAF mutations were independent from previously reported c-kit mutations. The classical V600E BRAF mutation was not found; instead a novel V600L was observed suggesting that the oncogenic event in OMM is different from that in skin melanoma. The low frequency of NRAS and BRAF mutations indicate that these genes are not common, but probable events in OMM pathogenesis, most likely independent of c-kit mutation.

    Item Type: Article
    Creators:
    1. Buery, R.R.
    2. Siar, C.H.
    3. Katase, N.
    4. Gunduz, M.
    5. Lefeuvre, M.
    6. Fujii, M.
    7. Inoue, M.
    8. Setsu, K.
    9. Nagatsuka, H.
    Journal or Publication Title: Oncology Reports
    Additional Information: ISI Document Delivery No.: 813QD Times Cited: 0 Cited Reference Count: 28 Cited References: Ashida A, 2009, INT J CANCER, V124, P862, DOI 10.1002/ijc.24048 Barker BF, 1997, ORAL SURG ORAL MED O, V83, P672, DOI 10.1016/S1079-2104(97)90318-8 Beadling C, 2008, CLIN CANCER RES, V14, P6821, DOI 10.1158/1078-0432.CCR-08-0575 Buery RR, 2010, J HARD TISSUE BIOL, V19, P57 Chernoff KA, 2009, CLIN CANCER RES, V15, P4288, DOI 10.1158/1078-0432.CCR-09-0280 Cohen Y, 2004, CLIN CANCER RES, V10, P3444, DOI 10.1158/1078-0432.CCR-03-0562 Curtin JA, 2006, J CLIN ONCOL, V24, P4340, DOI 10.1200/JCO.2006.06.2984 Curtin JA, 2005, NEW ENGL J MED, V353, P2135, DOI 10.1056/NEJMoa050092 Davies H, 2002, NATURE, V417, P949, DOI 10.1038/nature00766 Edwards RH, 2004, J MED GENET, V41, P270, DOI 10.1136/jmg.2003.016667 Flaherty KT, 2010, NEW ENGL J MED, V363, P809, DOI 10.1056/NEJMoa1002011 Hicks MJ, 2000, ORAL ONCOL, V36, P152, DOI 10.1016/S1368-8375(99)00085-8 Lennartsson J, 2005, STEM CELLS, V23, P16, DOI 10.1634/stemcells.2004-0117 Maldonado JL, 2003, J NATL CANCER I, V95, P1878, DOI 10.1093/jnci/djg123 Nagatsuka H, 2005, VIRCHOWS ARCH, V447, P710, DOI 10.1007/s00428-005-0016-1 Nazarian R, 2010, NATURE, V468, P973, DOI 10.1038/nature09626 Poynter JN, 2006, MELANOMA RES, V16, P267, DOI 10.1097/01.cmr.0000222600.73179.f3 Rivera RS, 2008, VIRCHOWS ARCH, V452, P27, DOI 10.1007/s00428-007-0524-2 Rivera RS, 2008, ONCOL REP, V19, P657 Saldanha G, 2006, CLIN CANCER RES, V12, P4499, DOI 10.1158/1078-0432.CCR-05-2447 Satyamoorthy K, 2003, CANCER RES, V63, P756 Satzger I, 2008, BRIT J CANCER, V99, P2065, DOI 10.1038/sj.bjc.6604791 Sekine S, 2009, VIRCHOWS ARCH, V454, P513, DOI 10.1007/s00428-009-0762-6 Sharma A, 2006, CANCER RES, V66, P8200, DOI 10.1158/0008-5472.CAN-06-0809 Smalley KSM, 2006, MOL CANCER THER, V5, P1136, DOI 10.1158/1535-7163.MCT-06-0084 Solit DB, 2006, NATURE, V439, P358, DOI 10.1038/nature04304 Wan PTC, 2004, CELL, V116, P855, DOI 10.1016/S0092-8674(04)00215-6 Wong CW, 2005, J CLIN PATHOL, V58, P640, DOI 10.1136/jcp.2004.022509 Buery, Rosario Rivera Siar, Chong Huat Katase, Naoki Gunduz, Mehmet Lefeuvre, Mathieu Fujii, Masae Inoue, Masahisa Setsu, Kojun Nagatsuka, Hitoshi Japan Society for the Promotion of Science22-00130; 21592326; 22791766 The study was supported by grants-in-aid from the Japan Society for the Promotion of Science fellow (no. 22-00130), the Scientific Research (no. 21592326), and the Young Scientists (no. 22791766). Spandidos publ ltd Athens
    Uncontrolled Keywords: Oral mucosal melanoma NRAS BRAF mutation immunohistochemistry kit gene b-raf activation inhibition expression subtypes kinase metastases resistance uncommon
    Subjects: R Medicine > RK Dentistry
    Divisions: Faculty of Dentistry
    Depositing User: Ms Nursyafiqah Abd Malek
    Date Deposited: 08 Jan 2013 11:42
    Last Modified: 08 Jan 2013 11:42
    URI: http://eprints.um.edu.my/id/eprint/4273

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