Allelic loss on chromosome 1 is associated with tumor progression of cervical carcinoma

Abstract

Alterations in chromosome 1 are common in human malignancies. The frequency of loss of heterozygosity (LOH) on chromosome 1 in cervical carcinoma and its clinical significance are not clearly understood. LOH on chromosome 1 was studied in 100 cervical carcinomas by the polymerase chain reaction (PCR) using 29 highly polymorphic microsatellite markers spaced approximately 10 centimorgans apart. Loci with high frequencies of LOH were identified and the findings were correlated with clinicopathologic characteristics. LOH on chromosome 1 at 1 or more loci was detected in 93% of tumors. The frequencies of LOH at locus D1S2829 (1p31), D1S2663 (1p36.3), and D1S2725 (1q25) exceeded 30%, and 12 other loci exhibited frequencies of LOH of 20-30%. Advanced stage tumors had a significantly higher percentage of informative microsatellite markers with LOH than early stage tumors. Of the 29 microsatellite markers studied, 4 loci had a significantly higher frequency of LOH in Stage III and IV tumors than in earlier stage tumors. Frequent aberrations on chromosome 1 in cervical carcinoma suggest that inactivation of tumor suppressor genes is important in cervical tumorigenesis. Higher frequencies of LOH in Stage III and IV tumors suggest that chromosome 1 changes are late events in cervical carcinoma. The findings of this study are consistent with earlier reports that suggest that tumor suppressor genes are present at 1p36.3 and 1p31. To the authors' knowledge, the high frequency of LOH mapped to 1q25 has not been reported previously. Its significance awaits further clarification.