SOMATIC DELETION MAPPING ON CHROMOSOME-10 AND SEQUENCE-ANALYSIS OF PTEN MMAC1 POINT TO THE 10Q25-26 REGION AS THE PRIMARY TARGET IN LOW-GRADE AND HIGH-GRADE GLIOMAS/

The l0q25-26 region between the dinucleotide markers D10S587 and D10S2 16 is deleted in glioblastomas and, as we have recently shown, in low- grade oligodendrogliomas. We further refined somatic mapping on 10q23- tel and simultaneously assessed the role of the candidate tumor suppre ssor gene PTEN/MMAC1 in glial neoplasms by sequence analysis of eight low-grade and 24 high-grade gliomas. These tumors were selected for pa rtial or complete loss of chromosome 10 based on deletion mapping with increased microsatellite marker density at 10q23-tel. Three out of ei ght (38%) low-grade and 3/24 (13%) high-grade gliomas exclusively targ et 10q25-26.We did not find a tumor only targeting 10q23.3, and most t umors (23/32, 72%) showed large deletions on 10q including both region s. The sequence analysis of PTEN/MMAC1 revealed nucleotide alterations in 1/8 (12.5%) low-grade gliomas in a tumor with LOH at l0q21-qtel an d in 5/21 (24%) high-grade gliomas displaying LOH that always included 10q23-26. Our refined mapping data point to the 10q25-26 region as th e primary target on 10q, an area that also harbors the DMBT1 candidate tumor suppressor gene. The fact that we find hemizygous deletions at 10q25-qtel in low-grade astrocytomas and oligodendrogliomas - two hist ologically distinct entities of gliomas - suggests the existence of a putative suppressor gene involved early in glial tumorigenesis.