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 10q25-26 region between the dinucleotide markers D10S587 and D10S216 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 suppressor gene PTEN/MMAC1 in glial neoplasms by sequence analysis of eight low-grade and 24 high-grade gliomas. These tumors were selected for partial or complete loss of chromosome 10 based on deletion mapping with increased microsatellite marker density at 10q23-tel. Three out of eight (38%) low-grade and 3/24 (13%) high-grade gliomas exclusively target 10q25-26. We did not find a tumor only targeting 10q23.3, and most tumors (23/32, 72%) showed large deletions on 10q including both regions. 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 and 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 the 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 histologically distinct entities of gliomas - suggests the existence of a putative suppressor gene involved early in glial tumorigenesis.
Neurosurgery and Department of Research, University Hospital, Basel, Switzerland.
D
D
Maier
Z
Z
Zhang
E
E
Taylor
M F
MF
Hamou
O
O
Gratzl
E G
EG
Van Meir
R J
RJ
Scott
A
A
Merlo
D019943:Amino Acid Substitution; D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics*; D004273:DNA, Neoplasm / Q000032:analysis / Q000235:genetics; D018900:Dinucleotide Repeats / Q000235:genetics; D017353:Gene Deletion; D016147:Genes, Tumor Suppressor / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D005910:Glioma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D019656:Loss of Heterozygosity; D009154:Mutation / Q000235:genetics; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D017422:Sequence Analysis, DNA; D012720:Severity of Illness Index; D025521:Tumor Suppressor Proteins
D004273:DNA, Neoplasm; D005819:Genetic Markers; D025521:Tumor Suppressor Proteins; D010744:Phosphoric Monoester Hydrolases; D017027:Protein Tyrosine Phosphatases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human