MDM2 splice variants in Oral Cancer

Sam, K.K.; Ng, K.L.P.; Ismail, S.M.; Zain, R.B.; Tay, K.K.; Cheong, S.C.; Chong, C.E.; Lim, P.; Teo, S.H. (2011) MDM2 splice variants in Oral Cancer. Oral Oncology, 47. S47-S47. ISSN 1368-8375

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      Abstract

      Introduction: MDM2 is a negative regulator of the p53 tumor suppressor protein. The presence of a variety of MDM2 splice variants have been reported in many different types of tumor and some have been shown to be associated with patient prognosis.Materials and methods: In this study, we demonstrated the occurrence of MDM2 splice variants in OSCC tissues. RNA was extracted from 45 OSCC tissues and 17 normal oral mucosa tissues and reverse transcribed into cDNA. Nested PCR was performed to amplify the MDM2 transcripts and the PCR amplicons were cloned into cloning vector pTZ57R/T and sequenced.Results: We demonstrated that 37/45 OSCC and 14/17 normal oral mucosa tissues contained MDM2 splice variants and a total of 34 transcript variants were found. Comparing with the reported splice variants in GenBank, four known variants, MDM2B, MDM2C, MDM2-EU2 and MDM2-PM2 were found in tumor samples with MDM2B being the most common variants found in our samples. None of these known variants were found in normal oral mucosa tissues. The other 30 transcript variants were novel, where 3 of these were present in both tumor and normal tissues, 23 were found only in tumor tissues and 4 were exclusive to normal oral mucosa tissue.Discussion: The common loss among the variants was sequences coding for the p53 binding domain, acidic domain, nuclear localization and nuclear export domains. In general, all 30 novel transcript variants were aberrantly spliced, however, interestingly, 9/23 aberrantly spliced variants in OSCC codes for an in-frame putative protein, suggesting that despite the aberrant splicing, these transcripts may still result in a functional protein and therefore further work to study how these splice variants affect MDM2 function directly or how they may affect other binding partners is needed.

      Item Type: Article
      Creators:
      1. Sam, K.K.
      2. Ng, K.L.P.
      3. Ismail, S.M.
      4. Zain, R.B.(Department of Oral Pathology and Oral Medicine and Periodontology, Faculty of Dentistry, University of Malaya)
      5. Tay, K.K.
      6. Cheong, S.C.
      7. Chong, C.E.
      8. Lim, P.
      9. Teo, S.H.
      Journal or Publication Title: Oral Oncology
      Additional Information: Sam, K. K. Ng, K. L. P. Ismail, S. M. Zain, R. Binti Tay, K. K. Cheong, S. C. Chong, Chan Eng Lim, Peng Teo, Soo-Hwang 3rd World Congress of the International-Academy-of-Oral-Oncology Jul 14-17, 2011 Singapore, SINGAPORE 1
      Uncontrolled Keywords: Oral squamous cell carcinoma, OSCC, lichenoid lesions, lichen planus, oral cancer, oral tumours, pemphigus, traumatic eosinophilic granuloma, aphthous ulcers, oral mucosal lesions, betel chewers mucosa, betel quid related lesions, betel quid, areca quid, tobacco quid, oral cancer screening, training and calibration, early detection, oral cancer awareness, biobanking, tissue bank, databank, oral cancer, tissue bank, research credibility, research ethics.
      Subjects: R Medicine > RK Dentistry > Oral surger
      Divisions: Faculty of Dentistry > Dept of Oral Pathology & Oral Medicine & Periodontology
      Depositing User: Prof. Dr. Rosnah Mohd Zain
      Date Deposited: 26 Jan 2012 12:25
      Last Modified: 11 Dec 2013 15:33
      URI: http://eprints.um.edu.my/id/eprint/2510

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