Kelly L. Price, M.S.

Thesis research performed under the guidence of Dr. William K. Kaufmann

ABSTRACT
    The development of genetic instability in human papillomavirus-induced carcinogenesis is hypothesized to be an early event, associated with loss of cell cycle checkpoint function and telomere erosion, while the reactivation of telomerase may be a later event, occurring after cells have acquired the necessary genetic alterations to become transformed.  Chromosome number instability, expression of cyclin A and B1, and telomerase activity were measured in cervical carcinomas and CIN precursor lesions.  Chromosome number instability was detected in 64% of high-grade CIN lesions and 80% of carcinomas.  Instability was detected in 11% of normal epithelia adjacent to high-grade lesions and in no low-grade CIN lesions.  There was no correlation between chromosome number instability and telomerase activity, nor cyclin overexpression.  However, telomerase activity was associated with cyclin A overexpression.  These results suggest that both telomerase reactivation and genetic instability are important in carcinogenesis, but the timing of each may affect how cancer develops.