Ma. Pershouse et al., SUPPRESSION OF TRANSFORMED PHENOTYPE AND TUMORIGENICITY AFTER TRANSFER OF CHROMOSOME-4 INTO U251 HUMAN GLIOMA-CELLS, Genes, chromosomes & cancer, 20(3), 1997, pp. 260-267
The development of primary human brain tumors, particularly glioblasto
ma multiforme (GBM), has been associated with a number of molecular an
d chromosomal abnormalities. In this study, a novel tumor suppressor l
ocus was identified and localized after the transfer of a human chromo
some 4 into U251 human GBM cells. Hybrid clones containing a transferr
ed neomycin-resistance tagged chromosome 4 revealed an inability to fo
rm tumors in nude mice and a greatly decreased efficiency of soft agar
ose colony formation. As a control, clones containing a transferred ch
romosome 2 were generated, and these retained the tumorigenic phenotyp
e of the parental U251 cells. The presence of the transferred chromoso
mes was demonstrated by gain of polymorphic loci and FISH analyses. Se
veral suppressed hybrid clones were shown to contain spontaneously red
uced versions of the transferred chromosome 4. A common region of the
fragmented chromosome 4 was retained among these clones that included
the epidermal growth factor locus at 4q24-26 and several adjacent mark
ers. The identification of a common fragment in the suppressed clones
suggests the presence of a tumor suppressor gene or genes in this regi
on, involved in glioma oncogenesis. (C) 1997 Wiley-Liss, Inc.