Correlation of telomere length to malignancy potential in non‑melanoma skin cancers

Yamada-Hishida, Hanae; Nobeyama, Yoshimasa; Nakagawa, Hidemi

doi:10.3892/ol.2017.7278

Cited by 4 publications

(6 citation statements)

References 33 publications

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“…Using Q-FISH for the determination of TL in neoplastic epidermal cells, Yamada-Hishida et al found that TL was decreased in BD and AK (both had relatively close TL) in relation to BCC and SCC, suggesting that TL estimation in NMSC reflects its biological behavior, such as the metastatic and invasive potential. Moreover, the authors suggested that SCC precursor lesions exhibit a different TL from those of SCC [78]. On the contrary, Wainwright et al examined BCC and TL in relation to normal skin and reported that telomeres from BCC samples had a variable range of TL (out of the 20 samples they examined 13, had an increased mean TL, while 7 had a shorter TL) [79].…”

Section: Telomere Length (Tl)mentioning

confidence: 99%

Current and Future Trends in Molecular Biomarkers for Diagnostic, Prognostic, and Predictive Purposes in Non-Melanoma Skin Cancer

Νikolouzakis

Falzone

Lasithiotakis

et al. 2020

JCM

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Skin cancer represents the most common type of cancer among Caucasians and presents in two main forms: melanoma and non-melanoma skin cancer (NMSC). NMSC is an umbrella term, under which basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and Merkel cell carcinoma (MCC) are found along with the pre-neoplastic lesions, Bowen disease (BD) and actinic keratosis (AK). Due to the mild nature of the majority of NMSC cases, research regarding their biology has attracted much less attention. Nonetheless, NMSC can bear unfavorable characteristics for the patient, such as invasiveness, local recurrence and distant metastases. In addition, late diagnosis is relatively common for a number of cases of NMSC due to the inability to recognize such cases. Recognizing the need for clinically and economically efficient modes of diagnosis, staging, and prognosis, the present review discusses the main etiological and pathological features of NMSC as well as the new and promising molecular biomarkers available including telomere length (TL), telomerase activity (TA), CpG island methylation (CIM), histone methylation and acetylation, microRNAs (miRNAs), and micronuclei frequency (MNf). The evaluation of all these aspects is important for the correct management of NMSC; therefore, the current review aims to assist future studies interested in exploring the diagnostic and prognostic potential of molecular biomarkers for these entities.

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Section: Telomere Length (Tl)mentioning

confidence: 99%

Current and Future Trends in Molecular Biomarkers for Diagnostic, Prognostic, and Predictive Purposes in Non-Melanoma Skin Cancer

Νikolouzakis

Falzone

Lasithiotakis

et al. 2020

JCM

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“…The relation of telomere length with the malignant potential of different NMSCs was analyzed in AK, BD, BCC and cSCC tumours and surroundings epidermal tissues by calculating the telomere centromere ratio (TCR), which reflects telomere length more accurately than other experimental procedures [77]. TCR values for cSCC were significantly lower than those for BD and AK (cSCC < BD < AK) and peritumoral epidermal cells had higher TCR values than tumour cells.…”

Section: Telomere and Telomerase Activity In Cutaneous Squamous Cementioning

confidence: 99%

“…TCR values for cSCC were significantly lower than those for BD and AK (cSCC < BD < AK) and peritumoral epidermal cells had higher TCR values than tumour cells. These findings demonstrated that tumour biological behaviour was intrinsically related to telomere length and that telomere shortening is consistent with the invasive progression [77].…”

Section: Telomere and Telomerase Activity In Cutaneous Squamous Cementioning

confidence: 99%

Telomeres and Telomerase in Cutaneous Squamous Cell Carcinoma

Ventura

Pellegrini

Cardelli

et al. 2019

IJMS

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The role of telomere biology and telomerase activation in skin cancers has been investigated in melanoma and basal cell carcinoma but limited evidence is available for cutaneous squamous cell carcinoma (cSCC). We will review the current knowledge on the role of telomere and telomerase pathway in cSCC pathogenesis. At the somatic level, both long and short telomere lengths have been described in cSCC. This telomere dichotomy is probably related to two different mechanisms of tumour initiation which determines two tumour subtypes. Telomere shortening is observed during the invasive progression from in situ forms of cSCC, such as Bowen’s disease (BD) and actinic keratosis (AK), to invasive cSCC. At the germline level, controversial results have been reported on the association between constitutive telomere length and risk of cSCC. Approximately 75–85% of cSCC tumours are characterized by a high level of telomerase activity. Telomerase activation has been also reported in AKs and BD and in sun-damaged skin, thus supporting the hypothesis that UV modulates telomerase activity in the skin. Activating TERT promoter mutations have been identified in 32–70% of cSCCs, with the majority showing the UV-signature. No significant correlation was observed between TERT promoter mutations and cSCC clinico-pathological features. However, TERT promoter mutations have been recently suggested to be independent predictors of an adverse outcome. The attention on telomere biology and telomerase activity in cSCC is increasing for the potential implications in the development of effective tools for prognostic assessment and of therapeutic strategies in patients with cutaneous cSCC.

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“…As a prognostic biomarker, tissue TL outperforms existing clinical risk parameters. Several studies have investigated the relationship between TL and clinical features in squamous cell carcinoma (SCC) [31][32][33]. In cancer tissues, TL is linked to risk factors for oesophageal SCC in consumers of alcohol [31] and to cytologic biomarkers for cervical cancer [32].…”

Section: Discussionmentioning

confidence: 99%

“…In cancer tissues, TL is linked to risk factors for oesophageal SCC in consumers of alcohol [31] and to cytologic biomarkers for cervical cancer [32]. Furthermore, in non-melanoma skin cancer, TL was found to be significantly lower in SCC than in basal cell carcinoma, Bowen's disease, or keratosis [33]. In summary, we have demonstrated that the tumour/normal TL ratio is abnormally low in patients with a poor prognosis, and this may be a critical event in progression of HNSCC.…”

Section: Discussionmentioning

confidence: 99%

Telomere shortening in head and neck cancer: association between DNA demethylation and survival

Yamada¹,

Misawa²,

Mima³

et al. 2021

J. Cancer

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A growing body of evidence indicates that telomere dysfunction is a biological marker of progression in several types of cancer. However, the association between head and neck squamous cell carcinoma (HNSCC) and telomere length (TL) remains unknown. We measured the absolute TL levels in a well-characterised dataset of 211 tumoral vs normal tissues obtained from the same patients by quantitative polymerase chain reaction assay. Normalised TL levels were significantly lower in tumour samples than in normal tissue (P < 0.001) and there was a positive correlation between tumour tissue and normal mucosal tissue (R 2 = 0.176, P < 0.001). We were able to distinguish two classes, one with a tumour/normal TL ratio ≤ 0.3 (38.4%), which showed clear telomere erosion, and the other with a tumour/normal TL ratio > 0.3 (61.6%), in which the TL was slightly shorter or longer than that in normal tissue. Notably, the tumour/normal TL ratio was correlated with the likelihood of disease recurrence (P = 0.002), the 5-hydroxymethylcytosine level (P = 0.043), and expression of the ten-eleven translocation (TET) gene (P = 0.043). Our findings show that TL shortening and subsequent low levels of 5-hydroxymethylcytosine and TET expression may contribute to development of HNSCC.

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Correlation of telomere length to malignancy potential in non‑melanoma skin cancers

Cited by 4 publications

References 33 publications

Current and Future Trends in Molecular Biomarkers for Diagnostic, Prognostic, and Predictive Purposes in Non-Melanoma Skin Cancer

Current and Future Trends in Molecular Biomarkers for Diagnostic, Prognostic, and Predictive Purposes in Non-Melanoma Skin Cancer

Telomeres and Telomerase in Cutaneous Squamous Cell Carcinoma

Telomere shortening in head and neck cancer: association between DNA demethylation and survival

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