Genetic abnormalities detected in ependymomas by comparative genomic hybridisation

Carter, M; Nicholson, James C.; Ross, Fiona; Crolla, John A.; Allibone, R; Balaji, V.; Perry, RH; Walker, David; Gilbertson, Richard J.; Ellison, DW

doi:10.1038/sj.bjc.6600180

Cited by 158 publications

(128 citation statements)

References 42 publications

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“…Although the relationships between ependymoma grade, specific chromosomal aberrations, 7,8,12,40 and patient outcome [3][4][5] are controversial, we were able to classify between supratentorial grade II and grade III tumors with 100% accuracy. The signature includes genes with relevance to oncogenic processes, ie, cellcycle control (cyclin D1, CDK5, MCM7), signal transduction (MAP2K3, MAPKAPK3, STAM), apoptosis (SIVA, BAX), tumor invasiveness (COL6A1, COL9A3, L1CAM), and angiogenesis (FGFR1).…”

Section: Discussionmentioning

confidence: 85%

“…For example, 30 to 50% of pediatric ependymomas display balanced comparative genomic hybridization profiles in comparison to only 10% in adults. 7,8,11 This finding suggests that the development of ependymomas at younger age is often independent of chromosomal instability. The recent histological ependymoma classification has thus far proven to be an unreliable predictor of clinical outcome and relationship between ependymoma grade and specific chromosomal aberrations is also controversial.…”

mentioning

confidence: 70%

“…For example, increased expression (more than twofold) was found concerning PRELP, EPHX1, FY, and HSPA6, all located on chromosomal arm 1q, which frequently showed copy number gains in ependymoma. 7 Correspondingly, genes from frequently deleted regions 7,8,11 were found weakly expressed (Ͻ0.5-fold), eg, COX7A2, COL10A1, and TCP1 from chromosome 6q; CNTFR, RAGA, TXN, AMBP, and HSPA5 from chromosome 9; TUBA2, PRDX2, and LCP1 from chromosome 13; and RANBP1, MCM5, EP300, G22P1, BZRP, and MAPK12 from chromosomal arm 22q. All 39 ependymomas analyzed in this study revealed a more than 10-fold expression of CLU, encoding for the glycoprotein clusterin (apolipoprotein J).…”

Section: Discussionmentioning

confidence: 99%

“…This might be because of NF2 gene deletions or mutations that are predominantly found in spinal cases 9,10,39 Moreover, the high NF2 gene expression levels found in 18 samples (more than threefold) might be explained by polysomies or gains of 22q that have been reported previously in ϳ50% of ependymomas. 39 Although some age-related immunohistochemical patterns 5 and genetic alterations 7,8,11 have been found associated with the outcome of ependymoma patients, the underlying biological mechanisms are still unclear. By using an age of 16 years as a cut-off point, the identified gene expression signature includes LDHB and STAM as highly expressed genes characteristic for younger patients.…”

Section: Discussionmentioning

confidence: 99%

“…The recent histological ependymoma classification has thus far proven to be an unreliable predictor of clinical outcome and relationship between ependymoma grade and specific chromosomal aberrations is also controversial. 2,7,8,11,12 By novel microarray technologies, the expression of thousands of genes can be studied simultaneously. In brain tumors, gene expression studies including astrocytic, 13,14 oligodendroglial, 15,16 as well as embryonal neuroepithelial tumors 17,18 have been performed recently.…”

mentioning

confidence: 99%

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Gene Expression Patterns in Ependymomas Correlate with Tumor Location, Grade, and Patient Age

Korshunov¹,

Neben²,

Wrobel³

et al. 2003

The American Journal of Pathology

145

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To elucidate the molecular events responsible for tumorigenesis and progression of ependymomas, we analyzed molecular alterations on the gene expression level in a series of newly diagnosed ependymal neoplasms (n ‫؍‬ 39). To this aim, tumor RNA was hybridized to microarrays comprising 2600 different genes with relevance to mitosis, cell-cycle control, oncogenesis, or apoptosis. For CLU, IGF-2, and RAF-1, which are apparent candidate genes because they had been previously described to be involved in tumorigenesis of other human malignancies, we found a high expression on the mRNA as well as the protein level. We identified gene expression signatures for the differentiation of tumors with respect to location, grade, and patient age. Spinal ependymomas were characterized by high-expression levels of HOXB5, PLA2G, and CDKN2A and tumors in young patients (<16 years of age) by high-expression levels of LDHB and STAM. Notably, we were able to classify supratentorial grade II and III tumors with 100% accuracy, whereas this did not apply for infratentorial Ependymal tumors arise from the ependymal lining of the cerebral ventricles and from the remnants of the central canal of the spinal cord. This neoplasm constitutes ϳ3 to 5% of all intracranial malignancies and is the third most common brain tumor in children and young adults. 1,2 In ependymomas, the morphological features and biological behavior vary considerably. Patients with spinal tumor location have usually a favorable prognosis after gross total resection, whereas local tumor progression is the predominant reason for death in patients with intracranial ependymomas, resulting in a 5-year overall survival of ϳ60%. [3][4][5] Because ependymomas are characterized by tremendous variability in clinical behavior, the understanding of the complex changes taking place at the genomic level might lead to more precise understanding of the tumor biology. Cytogenetic studies revealed numerous chromosomal aberrations in ependymomas. In particular, a 30 to 50% incidence of aberrations involving chromosome 22, including monosomy 22 as well as deletions of 22q, prevailed the most frequent finding. 6 -8 Recently, Hirose and co-workers 7 reported on different patterns of chromosomal abnormalities with respect to tumor location detected by comparative genomic hybridization. In intracranial tumors, gain of 1q and losses on 6q, 9, and 13 were frequent, whereas gains on chromosome 7 were recognized almost exclusively in spinal cord tumors and were associated with various other chromosomal aberrations including frequent loss of 22q, suggesting that intracranial and spinal cord ependymomas progress along substantially different pathways. As a hereditary form, neurofibromatosis type 2 is associated with spinal ependymomas, indicating a functional role of the NF2 tumor suppressor gene in these tumors. 9,10 In contrast to adults in which spinal tumors predominate, ϳ90% of all pediatric ependymomas are of intraSupported by the Bundesministerium fü r Bildung und Forschung (FKZ 01 KW 9937 and...

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