Differential alterations of the genes in the CDKN2A-CCND1-CDK4-RB1 pathway are associated with the development of head and neck squamous cell carcinoma in Indian patients.
OBJECTIVE
The aim of this study was to analyse the alterations of the genes in the CDKN2A/CCND1/CDK4/RB1 pathway in the G1-S phase of the cell cycle during development of head and neck squamous cell carcinoma (HNSCC).


METHODS
The alterations of these genes were analysed in 22 dysplastic lesions, 26 stage-I/II and 33 stage-III/IV HNSCC tumours of Indian patients.


RESULTS
The alterations [mutation, hypermethylation, homozygous deletion and loss of heterozygosity/microsatellite size alteration (LOH/MA)] in the CDKN2A were found to be highest in 57% of the samples, followed by CCND1 amplification and LOH/MA at the RB1 locus in 14% and 8.5% of the samples, respectively. No dominant CDK4 Arg24Cys mutation was seen in our samples. Comparatively high frequency of CDKN2A alterations (except homozygous deletion) was found in dysplastic head and neck lesions and remained almost constant or increased during progression of the tumour, whereas the homozygous deletion of CDKN2A and the alterations in CCND1 and RB1 genes were seen mainly in the later stages of the tumour.


CONCLUSIONS
Our study suggested that mutation/hypermethylation/allelic alterations (LOH/MA) of CDKN2A were associated with the development of dysplastic head and neck lesions. All the other alterations might provide some cumulative effect during progression of later stages of the tumour to have selective growth advantages.
Tripathi Bhar
Anusri
A
Department of Oncogene Regulation, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Calcutta 700026, India.
Banerjee
Soma
S
Chunder
Neelanjana
N
Roy
Anup
A
Sengupta
Arunava
A
Roy
Bidyut
B
Roychowdhury
Susanta
S
Panda
Chinmay Kumar
CK
D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D019938:Cyclin D1 / Q000235:genetics* / Q000378:metabolism; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases / Q000235:genetics* / Q000378:metabolism; D005260:Female; D019942:Genes, p16; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006801:Humans; D007194:India; D019656:Loss of Heterozygosity; D008297:Male; D008745:Methylation; D009154:Mutation; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins; D016160:Retinoblastoma Protein / Q000235:genetics*
D011518:Proto-Oncogene Proteins; D016160:Retinoblastoma Protein; D019938:Cyclin D1; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases