Abstract
BackgroundCyclin-dependent kinase 4 (CDK4) together with its regulatory subunit cyclin D1, governs cell cycle progression through G1 phase. Cyclin-dependent kinase inhibitors, including p16INK4A in turn regulate CDK4. In particular, deregulation of the p16/CDK4/cyclin D1 complex has been established in a variety of human tumors including gliomas, sarcomas, melanoma, breast and colorectal cancer. However, changes in CDK4 have rarely been observed.MethodIn this study we used a combination of PCR-SSCP and direct sequencing for mutational screening of CDK4. DNA was isolated from peripheral blood leukocyte of patients with squamous cell carcinoma of head and neck, for screening germline mutations in coding regions of CDK4.ResultsVariations observed in exon 2 and 5 were three missense mutations, g5051G > C (Ser52Thr), g5095G > C (Glu67Gln), g5906C > A, g5907C > G (Pro194Ser) and novel frame shift mutations g7321_23delTGA, g7121_7122insG, g7143delG in exon 7 and 3′UTR respectively.ConclusionIn conclusion, two novel mutations were found in N terminal domain which indicates that CDK4 mutation may play a major role in the development and progression of squamous cell carcinoma of head and neck.
Highlights
Cyclin-dependent kinase 4 (CDK4) together with its regulatory subunit cyclin D1, governs cell cycle progression through G1 phase
In conclusion, two novel mutations were found in N terminal domain which indicates that CDK4 mutation may play a major role in the development and progression of squamous cell carcinoma of head and neck
Blood samples from total of 380 patients with histological confirmed squamous cell carcinoma of head and neck, including oral cavity, pharynx and larynx were collected from National Oncology and Radiotherapy Institute (NORI), Pakistan Institute of Medical Sciences (PIMS) and Military Hospital (MH)
Summary
Cyclin-dependent kinase 4 (CDK4) together with its regulatory subunit cyclin D1, governs cell cycle progression through G1 phase. Cyclin-dependent kinase inhibitors, including p16INK4A in turn regulate CDK4. Deregulation of the p16/CDK4/cyclin D1 complex has been established in a variety of human tumors including gliomas, sarcomas, melanoma, breast and colorectal cancer. Cyclin-dependent kinases (Cdks) are serine/threonine kinases that regulate progression through cell cycle. D-type cyclin and their kinase partners, CDK4 and CDK6, coordinately phosphorylate the Rb protein, thereby releasing the transcription factor at G1 and progressions into the S phase occurs [3]. In addition to role in cell cycle, there is increasing evidence that Cdks, as well as cyclin and cyclin-dependent kinase inhibitors are important for other cellular functions, including cytoskeleton rearrangement and cell migration [4]. CDK4 is a potential oncogene, located on chromosome 12q13; mechanisms of activation could include gene amplification, over-
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