A PANEL OF TRANSFERABLE FRAGMENTS OF HUMAN-CHROMOSOME 11Q

Cytogenetic and molecular studies have implicated one or more tumor su ppressor genes on the long arm of human chromosome 11 in the malignant progression of several human solid tumors, including malignant melano ma and carcinomas of the breast, cervix, ovary, and lung. Microcell-me diated chromosome transfer of an intact copy of chromosome 11 into tum or cell lines has provided additional evidence of tumor suppressor gen e function in melanoma, breast cancer, and cervical cancer. However, s ublocalization of the region(s) conferring the tumor suppressive effec t has been difficult. To facilitate mapping of tumor suppressor gene(s ) on chromosome 11, we have generated a panel of 25 mouse donor cell l ines containing neo-tagged fragments of human chromosome 11q which can be transferred into cell lines to test for tumor suppressor activity. The chromosome fragments in these cell lines have been characterized by fluorescence in situ hybridization with probes to human DNA and to the centromere of chromosome 11, and also by analysis of microsatellit e markers spanning chromosome 11. Finally, to demonstrate the usefulne ss of these cell lines as donors for microcell-mediated chromosome tra nsfer, two fragments were transferred into the human melanoma cell lin e UACC 903. This panel of selectable subchromosomal fragments, derived from the long arm of human chromosome 11, will be useful for the regi onal localization of tumor suppressors and other genes by means of fun ctional assays.