Novel MDM2 splice variants identified from oral squamous cell carcinoma.
BACKGROUND
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).


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).


CONCLUSIONS
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.
Oral Cancer Research Team, Cancer Research Initiatives Foundation, 2nd Floor Outpatient Centre, Sime Darby Medical Centre, Subang Jaya, Malaysia.
Kin Kit
KK
Sam
Chai Phei
CP
Gan
Pei San
PS
Yee
Chan Eng
CE
Chong
Kue Peng
KP
Lim
Lee Peng
LP
Karen-Ng
Wei Sern
WS
Chang
Sheila
S
Nathan
Zainal Ariff Abdul
ZA
Rahman
Siti Mazlipah
SM
Ismail
Sok Ching
SC
Cheong
D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D016158:Genes, p53 / Q000235:genetics; D006801:Humans; D008207:Lymphatic Metastasis; D009061:Mouth Mucosa / Q000502:physiology*; D009062:Mouth Neoplasms / Q000235:genetics*; D009154:Mutation; D016133:Polymerase Chain Reaction; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D012326:RNA Splicing / Q000235:genetics*
C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2