Correlation among pathology, genetic and epigenetic profiles, and clinical outcome in oligodendroglial tumors
Journal
International Journal of Cancer
Journal Volume
124
Journal Issue
12
Pages
2872-2879
Date Issued
2009
Author(s)
Lee M.-J.
Wei C.-C.
Scaravilli F.
Tseng H.-M.
Abstract
Recent studies have revealed a correlation between specific genetic changes, such as loss of chromosome 1p and 19q, and sensitivity of oligodendroglial neoplasm to radiotherapy and chemotherapy; epigenetic changes also play an important role in some tumors. In this retrospective study, we analyzed chromosomal alterations in 17 loci and promoter methylation status of 8 tumor-related genes in 49 oligodendroglial tumors (29 WHO grade II and 11 WHO grade III oligodendrogliomas; 7 WHO grade II and 2 WHO grade III oligoastrocytomas) using quantitative microsatellite analysis and methylation-specific polymerase chain reaction and correlated this information with clinical data. We also performed immunohistochemical stains for Ki-67 and O (6)-methyl guanine-DNA methyl transferase. Our results showed that the frequency of deletions in regions on 1p, 9p, 10q, 17p and 19q were 71.4%, 26.5%, 6.1%, 69.4% and 89.8%, respectively. Promoter methylation was detected in p14, p15, p16, p53, p73, PTEN, MGMT and RASSF1A genes in 24.5%, 6.1%, 46.9%, 0%, 6.1%, 42.9%, 53.1% and 77.6% of tumors, respectively. Statistical analysis identified that 9p22 loss, p73 methylation and p15 methylation were independently associated with reduced overall survival, and Ki-67 labeling index (LI) ? 5%, 9p22 loss, no loss of 19q, p73 methylation, p14 methylation and unmethylated MGMT predicted shorter progression-free survival. Our findings suggest that the frequent deletion and hypermethylation of tumor-related genes may represent a mechanism of tumor development and progression and emphasize the importance of defining new molecular markers for predicting prognosis, tumor recurrence and therapeutic response in cancer management. ? 2009 UICC.
SDGs
Other Subjects
Ki 67 antigen; lomustine; methylated DNA protein cysteine methyltransferase; phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase; procarbazine; protein p14; protein p15; protein p16; protein p53; protein p73; Ras association domain family protein 1A; vincristine; DNA; DNA methyltransferase; Ki 67 antigen; MGMT protein, human; MIB1 protein, human; microsatellite DNA; polydeoxyribonucleotide synthase; tumor protein; tumor suppressor protein; ubiquitin protein ligase; adolescent; adult; aged; article; astrocytoma; cancer chemotherapy; cancer radiotherapy; cancer survival; child; chromosome 10q; chromosome 17p; chromosome 19q; chromosome 1p; chromosome 9p; chromosome deletion; clinical article; clinical feature; controlled study; DNA hypermethylation; DNA methylation; epigenetics; female; gene locus; glioblastoma; histopathology; human; human tissue; labeling index; male; microsatellite marker; oligodendroglioma; oncogene; overall survival; preschool child; priority journal; progression free survival; promoter region; school child; brain tumor; cancer staging; cell proliferation; chromosome aberration; enzyme immunoassay; genetic epigenesis; genetics; human chromosome; metabolism; middle aged; oligodendroglioma; pathology; polymerase chain reaction; retrospective study; survival rate; Adolescent; Adult; Aged; Aged, 80 and over; Brain Neoplasms; Cell Proliferation; Child; Child, Preschool; Chromosome Aberrations; Chromosomes, Human; DNA Methylation; DNA Modification Methylases; DNA Repair Enzymes; DNA, Neoplasm; Epigenesis, Genetic; Female; Humans; Immunoenzyme Techniques; Ki-67 Antigen; Male; Microsatellite Repeats; Middle Aged; Neoplasm Proteins; Neoplasm Staging; Oligodendroglioma; Polymerase Chain Reaction; Promoter Regions, Genetic; Retrospective Studies; Survival Rate; Tumor Suppressor Proteins; Ubiquitin-Protein Ligases; Young Adult
Type
journal article