Purpose Changes in MGMT promoter methylation, IDH1 and IDH2 mutation, and 1p/19q co-deletion status in gliomas between first and subsequent resections and their associated clinical factors are poorly described. In this study, we assayed these biomarkers in the clinical setting. Patients and methods We used multiplex ligation-dependent probe amplification to measure MGMT promoter methylation, IDH mutation status, and 1p/19q co-deletion in 45 paired tumor samples from patients undergoing resection and subsequent re-resections for gliomas. Results Molecular changes were present in 20 patients (44%). At least one molecular characteristic changed over time in 89% of patients with primary grade III tumors. Gliomas with IDH wild-type and/or non-co-deleted were stable, but IDH1 / 2 mutation and/or co-deletion were sometimes lost at the time of recurrence. In a multivariate analysis, adjuvant radiotherapy alone was independently associated ( P =0.02) with changes in molecular profile. Conclusion Molecular biomarkers change in gliomas during the course of the disease, most often MGMT methylation status. These changes in genetic profiles are related to adjuvant treatment with radiotherapy alone, which might be important for individualized treatment planning over the disease course.

We investigated bone marrow cells of 70 acute lymphoblastic leukemia children by conventional cytogenetics (CC), fluorescence in situ hybridization (FISH), and reverse transcription polymerase chain reaction (RT-PCR) methods. CC and RT-PCR for fusion genes BCR/ABL, MLL/AF4, E2A/PBX1, TEL/AML1 were performed at diagnosis in each patient. FISH was performed to verify the presence of fusion genes and MLL rearrangements and to estimate the percentage of abnormal cells. Karyotypes were obtained in 59 (84%) of 70 cases. Thirty-five (59%) of 59 cases revealed chromosome aberrations. Hyperdiploidy>50 chromosomes was present in nine cases, hyperdiploidy 47-50 chromosomes in six, pseudodiploidy in 15, and hypodiploidy in five. BCR/ABL was present in two cases, PBX1/E2A in two, and TEL/AML1 in 14. MLL/AF4 was not found, but the rearrangements of MLL gene were present in five children. The addition of RT-PCR and FISH to CC was of the utmost importance. One of two Ph translocations and one of two t(1;19) were first revealed by RT-PCR. Moreover, FISH showed the percentage of TEL/AML1(+) cells that turned to be an important prognostic factor. The outcome was the best for the children with hyperdiploidy>50 chromosomes without structural changes. It was also good for those with TEL/AML1 present in >or=80% of cells without chromosome aberrations. The presence of pseudodiploidy correlated with poor outcome. The outcome for patients with t(9;22)-BCR/ABL or 11q23-MLL rearrangement was the worst in study group. The presence of BCR/ABL caused eight times increase of risk of death; MLL rearrangements caused 12 times increase.

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