MTS1 CDK4I IS ALTERED IN CELL-LINES DERIVED FROM PRIMARY AND METASTATIC ORAL SQUAMOUS-CELL CARCINOMA/

The MTS1/CDK4I gene encodes a 16 kDa cyclin kinase inhibitor and maps to chromosome 9p21, Previous studies have suggested the presence of a major tumour suppressor gene at this locus which may be inactivated in head and neck squamous cell carcinoma (HNSCC). To determine the statu s of this gene in human primary and metastatic HNSCC, we examined the locus and its transcript for abnormalities by polymerase chain reactio n (PCR), Out of 14 cell lines studied, four had lost only exon 1, one had lost only exon 2, three had lost both exons 1 and 2, and none of t he remaining six lines expressed a normal p16 mRNA, These latter six c ell lines expressed p16 transcripts that had suffered deletions rangin g in size from 2 16 base pairs, In each case, deletions led to a chang e of reading frame. Furthermore, in two cases abnormalities in the MTS 1/CDK4I gene were identical in cells derived from metastatic tumours a s compared to cells derived independently from the corresponding prima ry tumour, The identical nature of mutations observed in primary tumou rs and metastases derived from the same patient provides strong eviden ce that inactivation of p16 function was an in vivo event.