Enhanced MYCN expression and lsochromosome 17q in pineoblastoma cell lines

Kees, Ursula R.; Biegel, Jaclyn A.; Ford, Jette; Ranford, P.R.; Peroni, Susanne E.; Hallam, Lavinia; Parmiter, Annette H.; Willoughby, M. L. N.; Spagnolo, Dominic V.

doi:10.1002/gcc.2870090209

Cited by 31 publications

(20 citation statements)

References 29 publications

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“…There is precedent for activation of an oncogene by promoter mutations in the absence of cytogenetic aberrations. For example, we have observed the activation of MYC-family genes in the absence of abnormal cytogenetics or gene ampli®cation (Kees et al, 1994(Kees et al, , 1998. Moreover, expression of the TAL1/SCL proto-oncogene is reported to be deregulated in T-ALL without translocation or gross deletion (Bash et al, 1995;Bernard et al, 1992;Macintyre 1992).…”

Section: A Model For Silencing Of Hox11 Expression In Normal Cells Ofmentioning

confidence: 95%

Multiple negative elements contribute to repression of the HOX11 proto-oncogene

1998

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The HOX11 proto-oncogene is normally expressed in embryogenesis where it directs the synthesis of the spleen. In adult tissues, HOX11 expression is silenced by an unknown mechanism. Aberrant expression of HOX11 occurs in T-cell acute lymphoblastic leukaemia (T-ALL), where it is thought to be involved in T-cell immortalization. The deregulated expression of HOX11 is frequently associated with chromosomal translocations which juxtapose a T-cell receptor (TCR) gene upstream of the HOX11 gene. In these cases, it is presumed that the activation of HOX11 expression results from bringing the gene under the control of TCR enhancer elements. However, activation of HOX11 also occurs in the absence of an associated translocation in both T-ALL and erythroleukaemia cells, implying that an alternative activation mechanism may exist. We hypothesized that HOX11 may be repressed in normal T-cells and erythroid cells by the action of negative elements which may be deleted or mutated in leukaemia. We therefore conducted a search for negative elements in the human HOX11 promoter which may function to silence its expression in normal cells of the haematopoietic lineages. Since little sequence of the HOX11 promoter was available, we began our investigation by sequencing over 4.5 kilobases of untranslated DNA from upstream of HOX11. The human sequence that overlaps with the 2.1 kb of murine Hox11 is highly conserved, suggesting that a large region of DNA upstream of HOX11 may have a regulatory function. We then used transfection assays to test the ability of portions of the promoter to drive transcription of a reporter gene. These studies identi®ed four negative elements. Two of them (NRE2 and NRE4) function in all cell lines tested, while the remaining two (NRE1 and NRE3) appear to be cell-type speci®c. The DNA sequences of three elements are conserved between the human and mouse HOX11/Hox11 promoters. We propose a model in which the combined action of these negative elements contributes to the overall repression of HOX11 expression in normal blood cells.

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Section: A Model For Silencing Of Hox11 Expression In Normal Cells Ofmentioning

confidence: 95%

Multiple negative elements contribute to repression of the HOX11 proto-oncogene

1998

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“…Cytogenetic and molecular data on pineal parenchymal tumors are sparse and have only been reported for nine pineocytomas (Rainho et al, 1992;Bello et al, 1993;Tsumanuma et al, 1995;Nozaki et al, 1998), and eight pineoblastomas or their cell lines (Sreekantaiah et al, 1989;Kees et al, 1994;Tsumanuma et al, 1995;Brockmeyer et al, 1997;Kees et al 1998). To date, no data are available for pineal parenchymal tumors of intermediate differentiation.…”

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confidence: 99%

Comparative genomic hybridization in pineal parenchymal tumors

Rickert

Simon

Bergmann

et al. 2000

Genes Chromosom. Cancer

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“…Among these are structural abnormalities of chromosome 1 (Griffin et al, 1988), 11 (Sreekantaiah et al, 1989 and 17q (Kees et al, 1994). A tumour-related locus on 17 p13 -distinct from p53 -was also reported for some paediatric neuroectodermal tumours (Biegel et al, 1992).…”

Section: Discussionmentioning

confidence: 99%

The RB1 gene mutation in a child with ectopic intracranial retinoblastoma

Onadim

Woolford²,

Kingston³

et al. 1997

Br J Cancer

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Summary The RB1 gene mutation was investigated in a child with ectopic intracranial retinoblastoma using DNA obtained from both the pineal and retinal tumours of the patient. A nonsense mutation in exon 17 (codon 556) of the RB1 gene was found to be present homozygously in both the retinal and the pineal tumours. The same mutation was present heterozygously in the DNA from the constitutional cells of the patient, proving it to be of germline origin. The initial mutation was shown to have occurred in the paternally derived RB1 allele. The mutation is in an area of the gene that encodes the protein-binding region known as the 'pocket' region and has been detected in other cases of retinoblastoma.

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Enhanced MYCN expression and lsochromosome 17q in pineoblastoma cell lines

Cited by 31 publications

References 29 publications

Multiple negative elements contribute to repression of the HOX11 proto-oncogene

Multiple negative elements contribute to repression of the HOX11 proto-oncogene

Comparative genomic hybridization in pineal parenchymal tumors

The RB1 gene mutation in a child with ectopic intracranial retinoblastoma

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