Functional and molecular analyses of 10q deletions in human gliomas

Extensive genomic deletions involving chromosome IO are the most common gen etic alteration in glioblastoma multiforme (GBM). To localize and examine t he potential roles of two chromosome arm 10q tumor suppressor regions, we u sed two independent strategies: mapping of allelic deletions, and functiona l analysis of phenotypic suppression after transfer of chromosome 10 fragme nts. By allelic deletion analysis, the region of 10q surrounding the MMAC/P TEN locus was shown to be frequently lost in GBMs but maintained in most lo w-grade astrocytic tumors. An additional region at 10q25 containing the DMB TI locus was lost in all grades of gliomas examined. The potential biologic al significance of these two regions was further assessed by examining micr ocell hybrids that contained various fragments of 10q. Somatic cell hybrid clones that retained the MMAC/PTEN locus have a less transformed phenotype with crones exhibiting an inability to grow in soft agarose. However, prese nce or absence of DMBTI did not correlate with any in vitro phenotype asses sed in our model system. These results support a model of molecular progres sion in gliomas in which the frequent deletion of 10q25-26 is an early even t and is followed by the deletion of the MMAC/PTEN during the progression t o high-grade GBMs. (C) 1999 Wiley-Liss, Inc.