Isochromosome 17q in primitive neuroectodermal tumors of the central nervous system

Biegel, Jaclyn A.; Rorke, Lucy B.; Packer, Roger J.; Sutton, Leslie N.; Schut, Luis; Bonner, Kathy; Emanuel, Beverly S.

doi:10.1002/gcc.2870010206

Cited by 154 publications

(80 citation statements)

References 18 publications

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“…The findings of gain of 17q with reciprocal loss of 17p in 26% of our cases of medulloblastoma are consistent with cytogenetic reports (Biegel et al, 1989;Bigner et al, 1997), with two smaller series of cases studied using CGH (Schütz et al, 1996;Reardon et al, 1997), and with findings of LOH on 17p (Cogen et al, 1990;Blaeker et al, 1996). The relative importance of 17p loss and 17q gain remains unclear.…”

Section: Discussionsupporting

confidence: 91%

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Comparative genomic hybridization and histological variation in primitive neuroectodermal tumours

et al. 1999

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SummaryThe objective of this study was to test the hypothesis that chromosomal imbalances in central nervous system primitive neuroectodermal tumours (PNETs) reflect site and histology. We used comparative genomic hybridization to study 37 cases of PNET, of which four were cerebral and 31 were medulloblastomas classified histologically as classic (n = 17) or nodular/desmoplastic (n = 14). Tumour immunophenotype was characterized with antibodies to neuroglial, mesenchymal and epithelial markers. Chromosomal imbalances were detected in 28 medulloblastomas (90%), and significant associations between tumour variants and genetic abnormalities were demonstrated. Aberrations suggesting isochromosome 17q were present in eight (26%) medulloblastomas, of which seven were classic variants. None of these cases, or a further six with gain of 17q, showed immunoreactivity for glial fibrillary acidic protein. Loss on 9q was found in six cases (19%), five of them nodular/desmoplastic. Loss of 22 occurred in four (13%), all classic medulloblastomas in young patients with a poor outcome and immunoreactivity for more than one epithelial or mesenchymal marker. Different patterns of imbalance were found in the cerebral PNETs. There were no abnormalities of chromosome 17, but all three cases with imbalance showed losses of 3p12.3-p14.

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Section: Discussionsupporting

confidence: 91%

“…Cytogenetic studies of medulloblastoma and other PNETs have identified several non-random chromosomal aberrations in a high proportion of cases (Biegel et al, 1989;Bhattachajee et al, 1997;Bigner et al, 1997). Of these, isochromosome 17q [i(17q)] is the most common, occurring in a third of cases overall (Mertens et al, 1994).…”

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confidence: 99%

Comparative genomic hybridization and histological variation in primitive neuroectodermal tumours

et al. 1999

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“…Numerous studies have described genetic rearrangements, for example, losses, gains and mutations of various chromosomal regions in medulloblastomas. Losses on chromosome 17p through i(17q) (Biegel et al, 1989) or unbalanced translocation and loss of heterozygosity (LOH) on chromosome 1q, 8p, 10q, 11, 16q and 17p was frequently found Kraus et al, 1996;Reardon et al, 1997). For many of these regions the target is still unknown.…”

Section: Introductionmentioning

confidence: 99%

SGNE1/7B2 is epigenetically altered and transcriptionally downregulated in human medulloblastomas

et al. 2007

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In a genome-wide screen using differential methylation hybridization (DMH), we have identified a CpG island within the 5 0 region and untranslated first exon of the secretory granule neuroendocrine protein 1 gene (SGNE1/ 7B2) that showed hypermethylation in medulloblastomas compared to fetal cerebellum. Bisulfite sequencing and combined bisulfite restriction assay were performed to confirm the methylation status of this CpG island in primary medulloblastomas and medulloblastoma cell lines. Hypermethylation was detected in 16/23 (70%) biopsies and 7/8 (87%) medulloblastoma cell lines, but not in nonneoplastic fetal (n ¼ 8) cerebellum. Expression of SGNE1 was investigated by semi-quantitative competitive reverse transcription-polymerase chain reaction and found to be significantly downregulated or absent in all, but one primary medulloblastomas and all cell lines compared to fetal cerebellum. After treatment of medulloblastoma cell lines with 5-aza-2 0 -deoxycytidine, transcription of SGNE1 was restored. No mutation was found in the coding region of SGNE1 by single-strand conformation polymorphism analysis. Reintroduction of SGNE1 into the medulloblastoma cell line D283Med led to a significant growth suppression and reduced colony formation. In summary, we have identified SGNE1 as a novel epigenetically silenced gene in medulloblastomas. Its frequent inactivation, as well as its inhibitory effect on tumor cell proliferation and focus formation strongly argues for a significant role in medulloblastoma development.

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“…The adult tumor is said to occur more often in the cerebellar hemispheres than the vermis and is more often desmoplastic in histology (Aragones et al, 1994;Frost et al, 1995;Prados et al, 1995). Karyotypic analysis of medulloblastoma nds frequent structural abnormalities, with chromosome 17 the most frequently affected (Biegel et al, 1989).…”

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confidence: 99%

Adult medulloblastoma: Multiagent chemotherapy

Greenberg¹

2001

Neuro-Oncology

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In this study, the records of 17 adult patients with medulloblastoma treated with craniospinal radiation and 1 of 2 multiagent chemotherapy protocols were reviewed for progression-free survival, overall survival, and toxicity, and the patients were compared with each other and with similarly treated children and adults. Records of patients treated at 3 institutions were reviewed. Seventeen medulloblastoma patients (11 female, 6 male) with a median age of 23 years (range, 18-47 years) were treated with surgery, craniospinal radiation (CSRT) plus local boost, and 1 of 2 adjuvant chemotherapy regimens. All tumors were infratentorial (10 in 4th ventricle and 7 in left or right hemisphere). Ten patients presented with hydrocephalus, and 7 of them were shunted. Eight patients had gross total resection, 7 had subtotal resection (>50% removed), and 2 had partial resection (<50% removed). Postoperatively, 3 patients had positive cytology and 3 had positive spinal MRI. Five patients were classi ed as good risk and 12 were classi ed as poor risk (Chang staging system). Ten patients were treated with the "Packer protocol," consisting of CSRT plus weekly vincristine followed by 8 cycles of cisplatin, lomustine, and vincristine. Seven patients were treated with the Pediatric Oncology Group (POG) protocol, consisting of alternating courses of cisplatin/etoposide and cyclophosphamide/vincristine, followed by CSRT. Eight of 17 patients relapsed, with all 8 relapsing at the primary site. Other relapse sites included the leptomeninges (5), bone (1), and brain (1). The estimated median relapse-free survival (Kaplan-Meier) for all patients was 48 months (95% con dence interval, >26 months to ¥). Median relapse-free survival for patients on the Packer protocol was 26 months, and for those on the POG regimen was 48 months (P = 0.410). Five of 10 on the Packer protocol were relapse-free, while 4 of 7 were relapse-free on the POG regimen. Two patients relapsed during chemotherapy and 6 relapsed after completing all therapy at 18, 18, 26, 30, 40, and 48 months. The estimated median survival of all patients was 56 months (95% con dence interval, 27 to ¥) with 11 patients alive; for the Packer protocol, median survival was 36 months, and for the POG protocol, it was 57 months (P = 0.058). The hazard ratio was 0 (95% con dence interval, 0 to ¥). Toxicity during the Packer protocol was moderately severe, with only 1 of 10 patients able to complete all therapy. Two patients had severe abdominal pain during CSRT + vincristine, and 5 had peripheral neuropathy during vincristine therapy. Hearing loss (>20 dB) occurred in 7, neutropenia (<500 µl) in 6, thrombocytopenia (<50,000 µl) in 6, nephrotoxicity (>25% ¯by creatinine clearance) in 2, and decreased pulmonary function (diffusing capacity for carbon monoxide ¯>40%) in 1. On the POG protocol, only 1 patient had persistent nausea and vomiting, 2 had peripheral neuropathy, and 3 had hearing de cit (>20 dB) or tinnitus. The POG and Packer protocols did not have a statistically signi cant differenc...

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Isochromosome 17q in primitive neuroectodermal tumors of the central nervous system

Cited by 154 publications

References 18 publications

Comparative genomic hybridization and histological variation in primitive neuroectodermal tumours

Comparative genomic hybridization and histological variation in primitive neuroectodermal tumours

SGNE1/7B2 is epigenetically altered and transcriptionally downregulated in human medulloblastomas

Adult medulloblastoma: Multiagent chemotherapy

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