C-myc oncogene expression in ocular melanomas

Royds, JA; Sharrard, R. M.; Parsons, M A; Lawry, J.; Rees, RC; Cottam, David W.; Wagner, Bart; Rennie, IG

doi:10.1007/bf00165947

Cited by 39 publications

(16 citation statements)

References 22 publications

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“…9 For example, c-myc can induce expression of D-type cyclins, 30 -32 and this protooncogene is commonly expressed in uveal melano- mas. 33,34 Further work is needed to determine whether c-myc may be responsible for deregulating cyclin D1 in these tumors.…”

Section: Discussionmentioning

confidence: 99%

Deregulation of the Rb and p53 Pathways in Uveal Melanoma

Brantley

Harbour

2000

The American Journal of Pathology

112

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Uveal melanoma is the most common primary eye cancer, yet its molecular pathogenesis is poorly understood. In this study, we investigated the immunohistochemical expression of proteins in the Rb and p53 tumor suppressor pathways in 33 uveal melanomas from enucleated eyes. Strong nuclear staining for Rb was present in most tumors. However, a few cases displayed weak nuclear staining and strong cytoplasmic staining (possibly indicating Rb mutation), and this aberrant staining correlated strongly with failed radiotherapy or thermotherapy before enucleation. Staining for cyclin D1 was positive in most tumors and was associated with advanced age and larger tumor size, which are both poor prognostic factors. Generally, immunostaining for p53 was weak (suggesting a lack of p53 mutations), although p53 positivity correlated strongly with staining for phosphorylated Rb, supporting the notion that inappropriate phosphorylation of Rb can induce p53. Strong immunostaining for MDM2, which can functionally block p53 activity, was observed in most tumors and correlated significantly with female sex. Strong cytoplasmic staining was observed for Bcl2, which can inhibit both p53-dependent and -independent apoptosis. We conclude that Rb and p53 are mutated infrequently in uveal melanoma , but their respective pathways may be functionally inactivated. Uveal melanoma is the most common primary malignancy of the eye, yet little is known about its molecular pathogenesis. In contrast to cutaneous melanoma in which significant advances have been made in understanding the molecular etiology, 1 no genes or tumor suppressor pathways have been convincingly linked to uveal melanoma. In addition, most evidence suggests that uveal melanoma differs etiologically from its cutaneous counterpart. Cytogenetic changes commonly found in cutaneous melanoma include loss of 1p, 6q, and 10q, and gain of chromosome 7, 1 whereas the most common changes in uveal melanoma are loss of 3p and 6q, and gain of 6p and 8q. [2][3][4] In addition, the p16/INK4a tumor suppressor locus on chromosome 9p21 is frequently deleted in cutaneous melanoma, 1 but it is rarely altered in uveal melanoma. [5][6][7][8] This void in our understanding of uveal melanoma is complicated by the fact that this tumor is rarely familial and is not amenable to genetic linkage analysis. Therefore, one approach to examining the molecular pathogenesis of uveal melanoma is to study the Rb and p53 tumor suppressor pathways, both of which are commonly disrupted in cancer. 9,10

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Section: Discussionmentioning

confidence: 99%

Deregulation of the Rb and p53 Pathways in Uveal Melanoma

Brantley

Harbour

2000

The American Journal of Pathology

112

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“…Cyclin D1 Unfavorable outcome/extraocular extension [15,16,105,106] Ki-67 and PCNA Ag Cell proliferation/epithelioid cell type/metastatic risk [101,[106][107][108][109][110] Oncogene c-Kit (CD177) Upregulated [111][112][113][114] Oncogene c-myc Improves survival [94,106,[115][116][117] p16, p27, p21 Present in uveal melanoma [14,16] p21-activated kinase (PAK) Invasion potential-related [118] PTEN tumor suppressor Loss of expression [119] Rb tumor suppressor Inactivated [16,97,120] Telomerase Upregulated [121,122] …”

Section: Cd95 and Faslmentioning

confidence: 99%

Proteomics in uveal melanoma research: opportunities and challenges in biomarker discovery

Pardo

Dwek

Zitzmann

2007

Expert Review of Proteomics

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Uveal melanoma (UM) is the most frequent primary intraocular tumor in adult humans. Despite the significant advances in diagnosis and treatment of UM in the last decades, the prognosis of UM sufferers is still poor. Metastatic liver disease is the leading cause of death in UM and can develop after a long disease-free interval, suggesting the presence of occult micrometastasis. Proteomics technology has opened new opportunities for elucidating the molecular mechanism of complex diseases, such as cancer. This article will review the recent developments in biomarker discovery for UM research by proteomics. In the last few years, the first UM proteomics-based analyses have been launched, yielding promising results. An update on recent developments on this field is presented.

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“…15 c-myc is expressed in uveal melanoma 16. Multiplication of chromosome 8 is common in uveal melanoma3 5 11 17 and has been associated with poor prognosis 18.…”

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confidence: 99%

c-myc, p53, and Bcl-2 expression and clinical outcome in uveal melanoma

Chana

Wilson

Cree

et al. 1999

British Journal of Ophthalmology

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Aims-Overexpression of c-myc protein has independent prognostic significance in a variety of primary and metastatic cutaneous melanomas which suggests a possible role for this gene in melanomagenesis. We have therefore examined the importance of this oncogene in uveal melanoma and studied the coexpression of two other gene products, Bcl-2 and p53, which might contribute to its eVect. Methods-The percentage of cells positive for nuclear c-myc expression was estimated by flow cytometric analysis of nuclei extracted from paraYn blocks. The expression of Bcl-2 and p53 protein was assessed by immunohistochemistry. A total of 71 tumours were studied and the results compared with survival with a mean follow up period of 6 years. Results-c-myc was expressed in >50% of the cells by 70% of the tumours, and was independently associated with improved survival in a Cox multiple regression model. Although Bcl-2 was expressed by the majority of the cells in 67% tumours, it was without eVect on prognosis. None of the cases studied showed convincing positivity for p53. Analysis of coexpression showed that the best survival was seen in c-myc+/Bcl-2+ tumours and the worst in c-myc−/Bcl-2− tumours. Conclusion-The finding of improved rather than reduced survival in c-myc positive tumours is at variance with skin melanoma. There was no evidence to suggest that c-myc was modulated by upregulation of Bcl-2 or p53 inactivation/ mutation. Although Bcl-2 is unlikely to have any eVect on tumour growth or metastasis, it could contribute to the general lack of susceptibility to apoptosis in these tumours. (Br J Ophthalmol 1999;83:110-114) Although uveal melanoma is the commonest tumour of the eye, it represents less than 1% of cancer registrations and is a good example of a "rare" tumour. However, it accounts for 13% of deaths from melanoma. Death is invariably due to metastatic disease.

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C-myc oncogene expression in ocular melanomas

Cited by 39 publications

References 22 publications

Deregulation of the Rb and p53 Pathways in Uveal Melanoma

Deregulation of the Rb and p53 Pathways in Uveal Melanoma

Proteomics in uveal melanoma research: opportunities and challenges in biomarker discovery

c-myc, p53, and Bcl-2 expression and clinical outcome in uveal melanoma

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