Evaluation of telomerase activity in cutaneous melanocytic proliferations

Miracco, Clelia; Pacenti, Lorenzo; Santopietro, Rosa; Laurini, Lorella; Biagioli, Maurizio; Luzi, Pietro

doi:10.1053/hupa.2000.9779

Cited by 31 publications

(26 citation statements)

References 30 publications

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“…Senescence is important in protecting cells against malignant transformation with age and all benign tumors are likely to be controlled by senescence signals (12). The role of the telomere pathway in melanocyte senescence is also apparent from work showing that telomerase activity increases steadily from benign nevi to dysplastic nevi to melanoma (36,37).…”

Section: Discussionmentioning

confidence: 98%

Nevus Size and Number Are Associated with Telomere Length and Represent Potential Markers of a Decreased Senescence In vivo

Bataille

Kato

Falchi³

et al. 2007

Cancer Epidemiology, Biomarkers &Amp; Prevention

122

132

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Nevus counts represent one of the strongest risk factors for melanoma. They appear in childhood and adolescence and involute from middle age onwards. Recent evidence has shown that nevus cells undergo oncogene-induced senescence involving the p16/retinoblastoma pathway. However, telomere length also influences senescence in proliferative somatic cells and varies between individuals. This study explores whether telomere length measured in white cells is associated with nevus count and size in 1,897 Caucasian women ages 18 to 79 years. Total body nevus counts were positively correlated with white cell telomere length (mean, 7.09 kbp; range, 5.09-9.37) after adjustment for age (P = 0.0001). Age-adjusted telomere length was also associated with nevus count for nevi above 5 mm in diameter (P = 0.04). Subjects in the top category for nevus count had an average age-adjusted telomere length 150 bp longer than those in the lowest category. The positive correlation between white cell telomere length and nevi number and size may reflect an increased replicative potential (reduced senescence) in individuals with longer telomeres, which may not be melanocyte specific. Understanding mechanisms influencing the induction and involution of nevi will not only help in understanding the pathophysiology of melanoma but should also shed light on the complex relationship between aging and cancer. (Cancer Epidemiol Biomarkers Prev 2007;16(7):1499 -502)

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Section: Discussionmentioning

confidence: 98%

Nevus Size and Number Are Associated with Telomere Length and Represent Potential Markers of a Decreased Senescence In vivo

Bataille

Kato

Falchi³

et al. 2007

Cancer Epidemiology, Biomarkers &Amp; Prevention

122

132

View full text Add to dashboard Cite

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“…Bypass of the pRB-dependent OIS barrier may permit melanocytes to proliferate until a p53-dependent replicative senescence checkpoint is activated. Normal melanocytes express very low levels of telomerase, as do neval melanocytes (Miracco et al, 2000), and so proliferative clones of oncogene-transformed melanocytes may arrest growth behind a p53-dependent DNA damage response that is triggered when telomeres have eroded to a deprotected state (Simpson et al, 2005; Soo et al, 2011). Thus, p53 serves to arrest the division of oncogene-transformed melanocytes that were not collected behind the pRB barrier.…”

Section: Discussionmentioning

confidence: 99%

A prognostic signature of defective p53‐dependent G1 checkpoint function in melanoma cell lines

Carson

Omolo

Chu

et al. 2012

Pigment Cell Melanoma Res

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Summary Melanoma cell lines and normal human melanocytes were assayed for p53-dependent G1 checkpoint response to ionizing radiation-induced DNA damage. Sixty six percent of melanoma cell lines displayed a defective G1 checkpoint. Checkpoint function was correlated with sensitivity to ionizing radiation with checkpoint-defective lines being radio-resistant. Microarray analysis identified 316 probes whose expression was correlated with G1 checkpoint function in melanoma lines (P≤0.007) including p53 transactivation targets CDKN1A, DDB2 and RRM2B. The 316 probe list predicted G1 checkpoint function of the melanoma lines with 86% accuracy using a binary analysis and 91% accuracy using a continuous analysis. When applied to microarray data from primary melanomas, the 316 probe list was prognostic of four year distant metastases-free survival. Thus, p53 function, radio-sensitivity and metastatic spread may be estimated in melanomas from a signature of gene expression.

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“…Telomerase activity has been reported in cutaneous melanomas, using the TRAP assay, with increasing values from normal skin to benign nevi and to dysplastic nevi and finally to melanoma [29]. An association between increased telomerase activity and worse prognostic features, namely, ulceration, vascular invasion, mitotic rate and Breslow thickness has been described in melanoma [18,32,81,91,100]. Furthermore, higher telomerase activity has also been associated with higher proliferation rate and early metastasis [100,104].…”

Section: Telomerase Promoter Mutations In Skin Cancersmentioning

confidence: 99%

Telomerase promoter mutations in cancer: an emerging molecular biomarker?

et al. 2014

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Cell immortalization has been considered for a long time as a classic hallmark of cancer cells. Besides telomerase reactivation, such immortalization could be due to telomere maintenance through the "alternative mechanism of telomere lengthening" (ALT) but the mechanisms underlying both forms of reactivation remained elusive. Mutations in the coding region of telomerase gene are very rare in the cancer setting, despite being associated with some degenerative diseases. Recently, mutations in telomerase (TERT) gene promoter were found in sporadic and familial melanoma and subsequently in several cancer models, notably in gliomas, thyroid cancer and bladder cancer. The importance of these findings has been reinforced by the association of TERT mutations in some cancer types with tumour aggressiveness and patient survival. In the first part of this review, we summarize the data on the biology of telomeres and telomerase, available methodological approaches and nonneoplastic diseases associated with telomere dysfunction. In the second part, we review the information on telomerase expression and genetic alterations in the most relevant types of cancer (skin, thyroid, bladder and central nervous system) on record, and discuss the value of telomerase as a new biomarker with impact on the prognosis and survival of the patients and as a putative therapeutic target.

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Evaluation of telomerase activity in cutaneous melanocytic proliferations

Cited by 31 publications

References 30 publications

Nevus Size and Number Are Associated with Telomere Length and Represent Potential Markers of a Decreased Senescence In vivo

Nevus Size and Number Are Associated with Telomere Length and Represent Potential Markers of a Decreased Senescence In vivo

A prognostic signature of defective p53‐dependent G1 checkpoint function in melanoma cell lines

Telomerase promoter mutations in cancer: an emerging molecular biomarker?

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