DELETION AND TRANSLOCATION OF CHROMOSOME 11Q13 SEQUENCES IN CERVICAL-CARCINOMA CELL-LINES

Molecular genetic studies on HeLa cell-derived nontumorigenic and tumo rigenic hybrids have previously localized the HeLa cell tumor-suppress or gene to the long arm of chromosome 11. Extensive molecular and cyto genetic studies on HeLa cells have shown chromosome band 11q13 to be r earranged in this cell line. To determine whether q13 rearrangement is a nonrandom event in cervical carcinomas, six different human papillo ma virus (HPV)-positive (HeLa, SiHa, Caski, C4-I, Me180, and Ms751) an d two different HPV-negative (C33A and HT3) cell lines were studied. L ong-range restriction mapping using a number of q13-specific probes sh owed molecular rearrangements within 75 kb of INT2 probe in three HPV- positive cell lines (HeLa, SiHa, and Caski) and in an HPV-negative cel l line (HT3). FISH using an INT2 YAC identified a breakpoint within th e sequences spanned by this YAC in two of the cell lines, HeLa and Cas ki. INT2 cosmid derived from this YAC showed deletion of cosmid sequen ces in two other cell lines, SiHa and C33A. These two cell lines, howe ver, retained cosmid sequences of Cyclin D1, a probe localized 100 kb proximal to INT2. Deletions being the hallmark of a tumor-suppressor g ene, we conclude that the 100-kb interval between the two cosmids migh t contain sequences of the cervical carcinoma tumor-suppressor gene.