1p and/or 19q loss of heterozygosity (LOH): a predictive marker in diffuse gliomas ?
aInstitute of Pathology, Berne, Switzerland, bDepartement of Neurosurgery, University of Berne, Berne, Switzerland
AIM: Several recent studies have shown that patients with anaplastic oligodendrogliomas (WHO-grade III) which show combined LOH 1p and 19q have an increased response rate to PCV chemotherapy and a longer duration of response. Their median survival time is 5 to 10 years. The aim of the current study was to analyse LOH 1p/19q in a larger population of patients with a diagnosis of diffuse glioma WHO-grade II-IV. METHODS: Using PCR, various microsatellite sequences on chromosome 1p and 19q of both tumor DNA and DNA extracted from leukocytes (normal reference) were amplified and subsequently analysed with comparative gel electrophoresis. RESULTS: Fifteen oligodendrogliomas WHO-grade II and III, 21 oligoastrocytomas WHO-grade II and III, 16 astrocytomas WHO-grade II and III and 14 glioblastomas WHO-grade IV were analysed using this test. Other types of tumors of the nervous system served as controls. The frequency of combined 1p and 19q loss was higher in oligodendrogliomas (73%) than in oligoastrocytomas (52%). Combined allelic loss was found in 2/15 astrocytomas, 1/14 glioblastomas and in none of the control cases (0/6). The study also showed that 5/14 (35%) glioblastomas had a 1p loss and 4/14 (28%) a 19q loss only. Genetic alterations found in 1p and 19q in diffuse gliomas were correlated with the clinical data including tumor location, contrast enhancement, response to chemotherapy and progression-free survival. CONCLUSION: LOH 1p/19q was found more frequently in patients who had initially been diagnosed with an oligodendroglioma or oligoastrocytoma based on contrast enhancing MRI. This diagnosis was confirmed by histology in each case. A correlation between certain tumor locations and LOH 1p/19q was not obvious except for the fact that tumors in the right side of the brain were more likely to show a LOH 1p/19q. The response to chemo- and radiotherapy as well as progression-free survival are currently being analysed with regard to the LOH 1p/19q status.
Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Nice, France; February 7 - 10, 2004; in oral session 796 (Genetic instability).