Expression of recessive alleles by chromosomal mechanisms in retinoblastoma

Cavenee, Webster K.; Dryja, Thaddeus P.; Phillips, Robert A.; Benedict, William F.; Godbout, Roseline; Gallie, Brenda L.; Murphree, A. Linn; Strong, Louise C.; White, R.

doi:10.1038/305779a0

Cited by 1,781 publications

(717 citation statements)

References 18 publications

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“…For example, in familial retinoblastoma (RB), patients are heterozygous for an inactivating mutation in the retinoblastoma tumor suppressor gene. RB tumors develop following bi-allelic inactivation of the RB gene (Cavenee et al, 1983;Dryja et al, 1984). As children born with a germline RB mutation require only one additional genetic alteration, the loss of the one remaining functional allele, the incidence of RB tumor formation is much higher and occurs at an earlier age than observed in the general population, where both RB alleles must be inactivated in the same cell for tumors to develop (Knudson, 1971).…”

Section: The Brain As a Specialized Ecosystemmentioning

confidence: 99%

The ecology of brain tumors: lessons learned from neurofibromatosis-1

Pong

Gutmann

2010

Oncogene

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Traditionally, cancer studies have primarily focused on mutations that activate growth or survival pathways in susceptible pre-neoplastic/neoplastic cells. However, recent research has revealed a critical role for nonneoplastic cells within the tumor microenvironment in the process of cancer formation and progression. In addition, the existence of regional and developmental variations in susceptible cell types and supportive microenvironments support a model of tumorigenesis in which the dynamic symbiotic relationship between neoplastic and non-neoplastic cell types dictate where and when cancers form and grow. In this review, we highlight advances in neurofibromatosis type 1 (NF1) genetically engineered mouse brain tumor (glioma) modeling to reveal how cellular and molecular heterogeneity in both the pre-neoplastic/ neoplastic and non-neoplastic cellular compartments contribute to gliomagenesis and glioma growth.

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Section: The Brain As a Specialized Ecosystemmentioning

confidence: 99%

The ecology of brain tumors: lessons learned from neurofibromatosis-1

Pong

Gutmann

2010

Oncogene

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“…Tumour-suppressor genes such as BRCAJ , RBI (Cavenee et al, 1983), BRCA2 (Gudmundsson et al, 1995), APC (Ichii et al, 1992) and VHL (Tory et al, 1989) have been studied in many families in which there is a germline mutation to those genes, and loss of the wild-type allele has been seen at high frequency in the tumours of patients carrying the mutation. All these genes therefore fulfil the criteria expected of tumoursuppressor genes, namely obeying Knudson's 'two-hit' hypothesis (Knudson, 1971), whereby one defective allele is inherited and the second is inactivated by loss of part or all of the wild-type chromosome (Ponder, 1988).…”

Section: Loss Of Heterozygosity Studies In Tumours From Patients Withmentioning

confidence: 99%

Li-Fraumeni syndrome – a molecular and clinical review

Varley

Evans²,

Birch³

1997

Br J Cancer

315

180

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“…In a DNA repair pathway, recombinational processes may act to maintain genetic stability, but if deregulated or increased, genomic instability and malignant transformation can result. Importantly, increased HR could be a mechanism involved in loss of heterozygosity which is frequently observed in tumor development and progression (Cavenee et al, 1983;Koufos et al, 1984;EyfjoÈ rd et al, 1995). Thus, suppression of spontaneous HR is a means by which p53 can maintain genome stability.…”

Section: Introductionmentioning

confidence: 99%

Dissociation of p53-mediated suppression of homologous recombination from G1/S cell cycle checkpoint control

et al. 2000

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The tumor suppressor p53 is considered as the guardian of the genome which is activated following genotoxic stress. In many cell types, p53 mediates G1 cell cycle arrest as the predominant cellular response. Inactivation of wild-type p53 leads to loss of G1/S checkpoint control and to genomic instability, including increased spontaneous homologous recombination (HR). To determine whether regulation of the G1/S checkpoint is required for suppression of HR, we assessed recombination events using a plasmid substrate that stably integrated into the genome of p53-null mouse ®broblasts. Exogenous expression of a temperature-sensitive p53 protein (Ala135 to Val), which had lost trans-activation function and could not regulate G1/S transition when in mutant conformation, reduced HR rates to the same extent as wild-type p53. Furthermore, a p53 construct with an alternatively-spliced carboxy terminus also retained this ability in the absence of both activities, G1/S control and non-sequence speci®c DNA binding as mediated by the carboxy terminus. Our data dissociate regulation of HR by p53 from its role as a cell cycle checkpoint protein.The results support a model which extends p53's role as a guardian of the genome to include transactivationindependent regulatory functions in DNA repair, replication and recombination. Oncogene (2000) 19, 632 ± 639.

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Expression of recessive alleles by chromosomal mechanisms in retinoblastoma

Cited by 1,781 publications

References 18 publications

The ecology of brain tumors: lessons learned from neurofibromatosis-1

The ecology of brain tumors: lessons learned from neurofibromatosis-1

Li-Fraumeni syndrome – a molecular and clinical review

Dissociation of p53-mediated suppression of homologous recombination from G1/S cell cycle checkpoint control

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