Comparative genetic analysis of metachronous anaplastic oligoastrocytomas with extended recurrence-free interval

Two metachronous anaplastic oligoastrocytomas with different cerebral locations were analyzed in a 51-year-old patient with an extended recurrence-free interval of 6 years and an a long survival of 9 years. Remarkably, the patient had not undergone adjuvant chemotherapy. Different cytogenetic and molecular techniques were performed including comparative genomic hybridization (CGH), fluorescence in situ hybridization (FISH), allelic loss analysis, sequencing of p53, p16(INK4a)/CDKN2A and p14(ARF), EGFRamplification studies, investigation of the DNA mismatch repair system as well as tumor clonality. Using CGH and FISH a profile of low accumulation of cytogenetic aberrations was found in the second tumor, with no significant increase in the percentage of hyperdiploid nuclei. Microsatellite analysis showed a common pattern of allelic losses at 1p36, 19q13 and 9p21. Both specimens were also similar in that they retained heterozygosity at 10q23-q24 and 13q14 and that they harbor neither EGFR amplification nor mutations of p53, p16(INK4a)/CDKN2A or p14(ARF). The only further alteration in the second tumor was an allelic loss at p53. The X-chromosome inactivation (HUMARA) analysis revealed a polyclonal pattern in both samples. Our data strongly suggest that the second anaplastic oligoastrocytoma developed as a distant relapse of the first tumor. Whether the paucity of accumulation of the observed genetic alterations might be associated with the unusually extended relapse-free time of the patient remains to be elucidated.