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High frequency of large spontaneous deletions of DNA in tumor-derived CHEF cells.
Proc. Natl. Acad. Sci. U.S.A..4 1, 1989;86(7):2306-10.
Kaden DA, Bardwell L, Newmark P, Anisowicz A, Skopek TR, Sager R.
Division of Cancer Genetics, Dana-Farber Cancer Institute, Boston, MA 02115.
Spontaneous mutations arising at the HPRT locus were examined in 126 mutants recovered from a series of six CHEF-derived cell lines. Altered restriction fragment patterns were characterized by Southern blot hybridization, and gene expression by RNA blot hybridization. Point mutants and gene-expression mutants predominated in the control (nontumorigenic) 18-1D-3 cell line and in two tumor-derived lines, one of which (16-2 Tuk 4) displayed a mutator phenotype. In the other three lines, the majority of mutants had large partial or whole gene deletions. These results suggest that mutant enzymes in DNA replication or repair play an important role in neoplastic progression by causing extensive deletions in DNA, including excision of genes that encode tumor-suppressor functions, and deletion of regulatory sequences in protooncogenes.