Abstract:
PURPOSE:Elongation of telomeres is necessary for tumor cell immortalization and senescence escape; neoplastic cells use to alternative pathways to elongate telomeres: telomerase reactivation or a telomerase-independent mechanism termed alternative lengthening of telomeres (ALT). Telomerase and ALT pathway has been explored in adult and pediatric gliomas and medulloblastomas (MDBs); however, these mechanisms were not previously investigated in MDBs metastatic at the onset. Therefore, we analyzed the activation of telomerase and ALT pathway in a homogenous cohort of 43 pediatric metastatic medulloblastomas, to investigate whether telomere elongation could play a role in the biology of metastatic MDB. METHODS:We evaluated telomeres length via telomere-specific fluorescence in situ hybridization (Telo-FISH); we assessed nuclear expression of ATRX by immunohistochemistry (IHC). H3F3A and TERT promoter mutations were analyzed by pyrosequencing, while UTSS methylation status was analyzed via methylation-specific-PCR (MS-PCR). RESULTS:H3F3A mutations were absent in all MDBs, 30% of samples showed ATRX nuclear loss, 18.2% of cases were characterized by TERT promoter mutations, while 60.9% harboured TERT promoter hyper-methylation in the UTSS region. Elongation of telomeres was found in 42.8% of cases. Metastatic MDBs control telomere elongation via telomerase activation (10.7%), induced by TERT promoter mutations in association with UTSS hyper-methylation, and ALT mechanism (32.1%), triggered by ATRX inactivation. Among non-metastatic MDBs, only 5.9% (1/17) showed ATRX nuclear loss with activation of ALT. CONCLUSIONS:Our metastatic cases frequently activate ALT pathway, suggesting that it is a common process for senescence escape in primary metastatic medulloblastomas. Furthermore, the activation of mechanisms for telomere elongation is not restricted to certain molecular subgroups in this high-risk group of MDBs.
journal_name
J Neurooncoljournal_title
Journal of neuro-oncologyauthors
Minasi S,Baldi C,Pietsch T,Donofrio V,Pollo B,Antonelli M,Massimino M,Giangaspero F,Buttarelli FRdoi
10.1007/s11060-019-03127-wsubject
Has Abstractpub_date
2019-05-01 00:00:00pages
435-444issue
3eissn
0167-594Xissn
1573-7373pii
10.1007/s11060-019-03127-wjournal_volume
142pub_type
杂志文章abstract:PURPOSE:We evaluated the outcomes after stereotactic radiosurgery (SRS) for patients who developed new or progressive brain disease regardless of whether they had no prior radiation, PCI, or WBRT. METHODS:We retrospectively identified 90 SCLC patients who had SRS between 1991 and 2018. Thirty-one patients had no evide...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-019-03224-w
更新日期:2019-08-01 00:00:00
abstract::Type 2 diabetes mellitus (DM) and obesity are known risk factors for poor outcomes in patients with systemic malignancies but are not well-studied in the brain tumor population. In this study we asked if type 2 DM and elevated body mass index (BMI) are independent risk factors for poor prognosis in patients with high-...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-011-0676-4
更新日期:2012-01-01 00:00:00
abstract:INTRODUCTION:Patterns of failure in patients with olfactory neuroblastoma (ONB) according to two surgical approaches, craniofacial resection (CFR) and endoscopic surgery (ENDO), have yet to be analyzed. METHODS:We retrospectively reviewed 28 patients with surgically treated ONB between January 1995 and October 2017. F...
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abstract:BACKGROUND:The purpose of this study is to map spatial metabolite differences across three molecular subgroups of glial tumors, defined by the IDH1/2 mutation and 1p19q-co-deletion, using magnetic resonance spectroscopy. This work reports a new MR spectroscopy based classification algorithm by applying a radiomics anal...
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更新日期:2018-09-01 00:00:00
abstract::To evaluate whether vigorous treatment is beneficial for patients with meningeal gliomatosis (MG) we reviewed the case records of 20 consecutive patients treated for a symptomatic MG in our center. All received systemic or intrathecal chemotherapy and six received additional cranial or spinal radiotherapy. Six patient...
journal_title:Journal of neuro-oncology
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journal_title:Journal of neuro-oncology
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journal_title:Journal of neuro-oncology
pub_type: 杂志文章,评审
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abstract::Malignant gliomas (MG) are very aggressive tumors. In an effort to improve the outcome, the patients receive multi-modal therapies such as surgery, radiation and chemotherapy (temozolomide followed in many cases by bevacizumab). The survivors are affected by multiple learning and memory deficits. Greater deterioration...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-016-2188-8
更新日期:2016-09-01 00:00:00
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journal_title:Journal of neuro-oncology
pub_type: 杂志文章
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更新日期:2009-08-01 00:00:00
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journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-009-9805-8
更新日期:2009-08-01 00:00:00
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pub_type: 杂志文章
doi:10.1007/s11060-018-03019-5
更新日期:2019-01-01 00:00:00
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journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1023/a:1006460827300
更新日期:2000-03-01 00:00:00
abstract::Antiangiogenic therapies for malignant gliomas often result in transient response, and recurrent disease is characterized by adoption of invasive and hypoxic phenotype. The notch signaling pathway is activated in gliomas, and augments cell migration and hypoxic response. Here we report a clinical study of the combinat...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-016-2263-1
更新日期:2016-12-01 00:00:00
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doi:10.1007/s11060-005-9111-z
更新日期:2006-08-01 00:00:00
abstract::The purpose of this study is to characterize the time course of N-isopropyl-p-[123I]-iodoamphetamine (123I-IMP) uptake of primary central nervous system lymphomas (PCNSL) comparing with those of other common brain tumors such as malignant gliomas and meningioma. Ten patients with PCNSL, 14 with malignant gliomas and 7...
journal_title:Journal of neuro-oncology
pub_type: 临床试验,杂志文章
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更新日期:2003-02-01 00:00:00
abstract::The relation between hospital volume and outcomes for patients with glioblastoma is unknown. We undertook this study to determine the effect of hospital volume on treatment received and its effect on survival in patients with glioblastoma. We included patients from the National Cancer Database diagnosed with a gliobla...
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更新日期:2017-12-01 00:00:00
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更新日期:2014-06-01 00:00:00
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journal_title:Journal of neuro-oncology
pub_type: 临床试验,杂志文章
doi:10.1023/a:1006201909435
更新日期:1999-08-01 00:00:00
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pub_type: 杂志文章,评审
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更新日期:2010-01-01 00:00:00
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pub_type: 杂志文章
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更新日期:2021-01-04 00:00:00
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journal_title:Journal of neuro-oncology
pub_type: 杂志文章,多中心研究,随机对照试验
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更新日期:2018-05-01 00:00:00
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journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1023/b:neon.0000013488.52742.b4
更新日期:2004-01-01 00:00:00
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journal_title:Journal of neuro-oncology
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更新日期:2019-07-01 00:00:00
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journal_title:Journal of neuro-oncology
pub_type: 临床试验,杂志文章,多中心研究
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更新日期:1998-03-01 00:00:00
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journal_title:Journal of neuro-oncology
pub_type: 杂志文章
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更新日期:2006-09-01 00:00:00
abstract::Bevacizumab has been reported to cause diffusion restriction in the tumor bed of patients with malignant gliomas. This study evaluated prolonged diffusion restriction, in the corpus callosum (CC), of patients with malignant brain tumors treated with bevacizumab. We retrospectively reviewed our database of patients tre...
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更新日期:2014-05-01 00:00:00