Allelic Loss and Microsatellite Alterations of Chromosome 3p14.2 Are More Frequent in Recurrent Cervical Dysplasias

作者: Eugenia A. Michalopulos , Raheela Ashfaq , Robert L. Coleman , William Robinson , W. Michael Lin

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摘要: Epidemiological studies have documented the unpredictable clinical progression or recurrence of cervical dysplasia. Recent studies shown several molecular changes in cancers and their associated dysplasia. We conducted molecular analyses on a retrospectively ascertained cohort of recurrent nonrecurrent dysplasia cases an attempt to define biomarkers to predict progressive or recurrent disease. Cases were chosen if long-term follow-up (3–5 years after conization) biopsy confirmation available. Paraffin-embedded, postconization tissues from 19 18 nonrecurrent dysplasias analyzed. Human papillomavirus (HPV) was identified by PCR for general type-specific (HPV-16 HPV-18) primers. Allelotyping analysis performed by multiplex PCR using panel of 16 microsatellite markers targeting putative tumor suppressor gene regions chromosomes 3p, 5p, 6p, 9p, 11q, 17p. The overall rate of HPV infection similar both groups. In allelotyping analysis, loss heterozygosity at fragile histidine triad region in 3p14.2 significantly higher group than the nonrecurrent ( P = 0.005). Furthermore, microsatellite alterations (MAs) more frequent recurrent group (mean MA index, 0.254) as compared with group (mean 0.085; 0.0025). These findings suggest that status alone does not recurrence loss of region may represent a potential biomarker predicting recurrence. Frequent MAs the recurrent underlying genomic instability that creates susceptibility allelic loss, thus increasing risk for recurrence progression.

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