Novel MDM2 splice variants identified from oral squamous cell carcinoma

Kin Kit Sam, Chai Phei Gan, Pei San Yee, Chan Eng Chong, Kue Peng Lim, Lee Peng Karen-Ng, Wei Sern Chang, Sheila Nathan, Zainal Ariff Abdul Rahman, Siti Mazlipah Ismail, Sok Ching Cheong

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Introduction: The presence of a variety of MDM2 splice variants has been reported in a range of different tumor types and is associated with poor patient prognosis. Furthermore, several MDM2 variants have been shown to have oncogenic properties. Despite this, MDM2 splice variants have not been comprehensively characterized in oral squamous cell carcinoma (OSCC). Materials and methods: MDM2 splice variants were identified by polymerase chain reaction (PCR), using cDNA from 55 OSCC and 20 normal oral mucosa (NOM) tissues. MDM2 amplicons from the polymerase chain reactions were cloned and sequenced. The associations between the presence of MDM2 splice variants as well as the types of MDM2 splice variants with OSCC and patient clinico-pathological data was examined using Fisher Exact and Chi-square tests. Results: Thirty-eight MDM2 splice variants were identified from both OSCC and NOM tissues, where the majority (30/38) were exclusively detected in OSCC. Some of these variants were similar to those reported in other cancers whilst 14 novel MDM2 splice variants predicted to code for proteins were also identified. The majority of these variants retained their RING binding domain but had lost the p53 binding site. The presence of MDM2 splice variants was significantly associated with OSCC and increased the risk of OSCC development (OR = 9.98; 95% CI = 2.94-33.90). Conclusion: MDM2 splice variants were identified in OSCC at a high frequency and were significantly associated with OSCC development. This suggests that MDM2 splice variants may play an important role in oral carcinogenesis and the functional role of these variants in OSCC should be examined further.

Original languageEnglish
Pages (from-to)1128-1135
Number of pages8
JournalOral Oncology
Volume48
Issue number11
DOIs
Publication statusPublished - Nov 2012

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Squamous Cell Carcinoma
Mouth Mucosa
Polymerase Chain Reaction
Chi-Square Distribution
Neoplasms
Carcinogenesis
Complementary DNA
Binding Sites

Keywords

  • MDM2
  • Oral squamous cell carcinoma
  • p53
  • Splice variants

ASJC Scopus subject areas

  • Oncology
  • Oral Surgery
  • Cancer Research

Cite this

Sam, K. K., Gan, C. P., Yee, P. S., Chong, C. E., Lim, K. P., Karen-Ng, L. P., ... Cheong, S. C. (2012). Novel MDM2 splice variants identified from oral squamous cell carcinoma. Oral Oncology, 48(11), 1128-1135. https://doi.org/10.1016/j.oraloncology.2012.05.016

Novel MDM2 splice variants identified from oral squamous cell carcinoma. / Sam, Kin Kit; Gan, Chai Phei; Yee, Pei San; Chong, Chan Eng; Lim, Kue Peng; Karen-Ng, Lee Peng; Chang, Wei Sern; Nathan, Sheila; Rahman, Zainal Ariff Abdul; Ismail, Siti Mazlipah; Cheong, Sok Ching.

In: Oral Oncology, Vol. 48, No. 11, 11.2012, p. 1128-1135.

Research output: Contribution to journalArticle

Sam, KK, Gan, CP, Yee, PS, Chong, CE, Lim, KP, Karen-Ng, LP, Chang, WS, Nathan, S, Rahman, ZAA, Ismail, SM & Cheong, SC 2012, 'Novel MDM2 splice variants identified from oral squamous cell carcinoma', Oral Oncology, vol. 48, no. 11, pp. 1128-1135. https://doi.org/10.1016/j.oraloncology.2012.05.016
Sam KK, Gan CP, Yee PS, Chong CE, Lim KP, Karen-Ng LP et al. Novel MDM2 splice variants identified from oral squamous cell carcinoma. Oral Oncology. 2012 Nov;48(11):1128-1135. https://doi.org/10.1016/j.oraloncology.2012.05.016
Sam, Kin Kit ; Gan, Chai Phei ; Yee, Pei San ; Chong, Chan Eng ; Lim, Kue Peng ; Karen-Ng, Lee Peng ; Chang, Wei Sern ; Nathan, Sheila ; Rahman, Zainal Ariff Abdul ; Ismail, Siti Mazlipah ; Cheong, Sok Ching. / Novel MDM2 splice variants identified from oral squamous cell carcinoma. In: Oral Oncology. 2012 ; Vol. 48, No. 11. pp. 1128-1135.
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abstract = "Introduction: The presence of a variety of MDM2 splice variants has been reported in a range of different tumor types and is associated with poor patient prognosis. Furthermore, several MDM2 variants have been shown to have oncogenic properties. Despite this, MDM2 splice variants have not been comprehensively characterized in oral squamous cell carcinoma (OSCC). Materials and methods: MDM2 splice variants were identified by polymerase chain reaction (PCR), using cDNA from 55 OSCC and 20 normal oral mucosa (NOM) tissues. MDM2 amplicons from the polymerase chain reactions were cloned and sequenced. The associations between the presence of MDM2 splice variants as well as the types of MDM2 splice variants with OSCC and patient clinico-pathological data was examined using Fisher Exact and Chi-square tests. Results: Thirty-eight MDM2 splice variants were identified from both OSCC and NOM tissues, where the majority (30/38) were exclusively detected in OSCC. Some of these variants were similar to those reported in other cancers whilst 14 novel MDM2 splice variants predicted to code for proteins were also identified. The majority of these variants retained their RING binding domain but had lost the p53 binding site. The presence of MDM2 splice variants was significantly associated with OSCC and increased the risk of OSCC development (OR = 9.98; 95{\%} CI = 2.94-33.90). Conclusion: MDM2 splice variants were identified in OSCC at a high frequency and were significantly associated with OSCC development. This suggests that MDM2 splice variants may play an important role in oral carcinogenesis and the functional role of these variants in OSCC should be examined further.",
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AU - Karen-Ng, Lee Peng

AU - Chang, Wei Sern

AU - Nathan, Sheila

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AU - Ismail, Siti Mazlipah

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