ALLELOTYPE ANALYSIS OF CERVICAL-CARCINOMA

To identify the genetic events which may play a role in the developmen t of cervical carcinoma, we performed a detailed allelotype analysis u tilizing DNA from 53 primary tumors and corresponding normal cells and 57 polymorphic probes mapped to each of the chromosomal arms, excludi ng the short arms of the acrocentric chromosomes. Loss of heterozygosi ty (LOH) of >25% was observed at sites on 11 chromosomal arms, which i ncluded 1q (26%), 3p (35%), 3q (31%), 4q (46%), 5p (53%), 5q (38%), 6p (28%), 10q (28%), 11p (42%), 18p (38%), and Xq (26%). The most freque nt LOH was noted on 4q (ADH3) and 5p (D5S19), suggesting that loss of candidate tumor suppressor genes on these chromosomal arms may play a role in the development of cervical carcinoma. The two sites of deleti ons identified on 5p and Xq represent novel candidate tumor suppresser gene sites which have so far not been reported in any other tumor typ e. Human papilloma virus status did not correlate with any of the site s which showed frequent LOH. TP53 mutation analysis by single-strand c onformation polymorphism analysis was performed in 17 tumors that eith er showed 17p deletions (TP53, D17S5, or D17S28) or were human papillo ma virus negative. One of the 7 human papilloma virus negative tumors, which also showed LOH at the D17S28 locus, had a mutation in exon 5. This study represents the first comprehensive genetic analysis of this cancer and identifies several novel features of significance to genet ic etiology of cervical carcinoma.