https://scholars.lib.ntu.edu.tw/handle/123456789/434489
標題: | Genetic and Epigenetic Alterations in Primary-Progressive Paired Oligodendroglial Tumors | 作者: | LU-TING KUO SHAO-YU TSAI Chang C.-C. KUAN-TING KUO ABEL PO-HAO HUANG JUI-CHANG TSAI Tseng H.-M. MENG-FAI KUO YONG-KWANG TU |
公開日期: | 2013 | 卷: | 8 | 期: | 6 | 來源出版物: | PLoS ONE | 摘要: | The aim of the present study was to identify genetic and epigenetic alterations involved in the progression of oligodendroglial tumors. We characterized 21 paired, World Health Organization (WHO) grade II and III oligodendroglial tumors from patients who received craniotomies for the partial or complete resection of primary and secondary oligodendroglial tumors. Tumor DNA was analyzed for alterations in selected genetic loci (1p36, 9p22, 10q23-24, 17p13, 19q13, 22q12), isocitrate dehydrogenase 1 (IDH1), isocitrate dehydrogenase 2 (IDH2) and the CpG island methylation status of critical tumor-related genes (MGMT, P16, DAPK, PTEN, RASSF1A, Rb1). Alterations of these markers were common early in the tumorigenesis. In the primary tumors we identified 12 patients (57.1%) with 1p36 deletions, 17 (81.0%) with 19q13 deletions, 9 (42.9%) with 1p36/19q13 codeletions, 11 (52.3%) with 9p22 deletions, and 12 (57.1%) with IDH1 mutation. Epigenetic analysis detected promoter methylation of the MGMT, P16, DAPK, PTEN, RASSF1A, and Rb1 genes in 38.1%, 19.0%, 38.1%, 33.3%, 66.7%, and 14.3% of primary tumors, respectively. After progression, additional losses of 1p, 9p, 10q, 17p, 19q and 22q were observed in 3 (14.3%), 1 (4.8%), 3 (14.3%), 2 (9.5%), 1 (4.8%) and 3 (14.3%) cases, respectively. Additional methylations of the MGMT, P16, DAPK, PTEN, RASSF1A, and RB1 promoters was observed in 4 (19.0%), 2 (9.5%), 0 (0%), 6 (28.6%), 2(9.5%) and 3 (14.3%) cases, respectively. The status of IDH1 mutation remained unchanged in all tumors after progression. The primary tumors of three patients with subsequent progression to high-grade astrocytomas, all had 9p deletion, intact 1p, intact 10q and unmethylated MGMT. Whether this may represent a molecular signature of patients at-risk for the development of aggressive astrocytomas needs further investigation. ? 2013 Kuo et al. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84879477039&doi=10.1371%2fjournal.pone.0067139&partnerID=40&md5=7018ee302a6cbdb30354fd900d20b241 https://scholars.lib.ntu.edu.tw/handle/123456789/434489 |
ISSN: | 1932-6203 | DOI: | 10.1371/journal.pone.0067139 | SDG/關鍵字: | antineoplastic agent; carmustine; cisplatin; DNA; isocitrate dehydrogenase 1; isocitrate dehydrogenase 2; lomustine; procarbazine; temozolomide; vincristine; vincristine sulfate; adult; aged; article; astrocytoma; cancer radiotherapy; cancer surgery; carcinogenesis; chromosome 10q; chromosome 17p; chromosome 19q; chromosome 1p; chromosome 22q; chromosome 9p; chromosome deletion; chromosome loss; clinical article; CpG island; craniotomy; DAPK gene; DNA methylation; epigenetics; female; gene locus; gene mutation; glioblastoma; human; human tissue; longitudinal study; male; MGMT gene; oligodendroglioma; P16 gene; promoter region; PTEN gene; RASSF1A gene; Rb1 gene; tumor growth; Adult; Aged; Base Sequence; Brain Neoplasms; Disease Progression; DNA Methylation; DNA Mutational Analysis; Epigenesis, Genetic; Female; Humans; Isocitrate Dehydrogenase; Longitudinal Studies; Male; Middle Aged; Molecular Sequence Data; Oligodendroglioma; Promoter Regions, Genetic; Real-Time Polymerase Chain Reaction; Treatment Outcome; Young Adult |
顯示於: | 醫學系 |
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