Telomere Length in Neoplastic and Nonneoplastic Tissues of Patients with Familial and Sporadic Papillary Thyroid Cancer

Capezzone, Marco; Cantara, Silvia; Marchisotta, Stefania; Busonero, Giulia; Formichi, Caterina; Benigni, Michele; Capuano, Serena; Toti, Paolo; Pazaitou‐Panayiotou, Kalliopi; Caruso, Giuseppe; Carli, Anton Ferdinando; Palummo, Nazzareno; Pacini, Furio

doi:10.1210/jc.2011-1003

Cited by 31 publications

(38 citation statements)

References 17 publications

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“…No mutations were detected in medullary thyroid carcinomas, as described by Killela et al 3 , nor in normal thyroid and benign lesions, such as goitre, adenomas or thyroiditis; this finding fits with previous studies that reported telomerase expression in malignant lesions and not in normal tissue or hyperplastic lesions 8,9 . TERT mutations were associated with clinicopathological features (older age, increased tumour size and a b male gender), but, after histotype stratification, these associations were only maintained in cPTC.…”

Section: Resultssupporting

confidence: 91%

Frequency of TERT promoter mutations in human cancers

et al. 2013

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Reactivation of telomerase has been implicated in human tumorigenesis, but the underlying mechanisms remain poorly understood. Here we report the presence of recurrent somatic mutations in the TERT promoter in cancers of the central nervous system (43%), bladder (59%), thyroid (follicular cell-derived, 10%) and skin (melanoma, 29%). In thyroid cancers, the presence of TERT promoter mutations (when occurring together with BRAF mutations) is significantly associated with higher TERT mRNA expression, and in glioblastoma we find a trend for increased telomerase expression in cases harbouring TERT promoter mutations. Both in thyroid cancers and glioblastoma, TERT promoter mutations are significantly associated with older age of the patients. Our results show that TERT promoter mutations are relatively frequent in specific types of human cancers, where they lead to enhanced expression of telomerase.

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Section: Resultssupporting

confidence: 91%

Frequency of TERT promoter mutations in human cancers

et al. 2013

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“…A recent study by Capezzone and colleagues reported telomerase activity in most sporadic and familial malignant thyroid tumours as well as in some adenomas [15]. Telomerase activity was not observed in hyperplastic nodules or in normal thyroid tissue from patients with sporadic PTC [15]. In summary, the aforementioned findings suggest that telomerase activity may be associated with a more aggressive clinical behaviour of thyroid tumours.…”

Section: Telomerase Promoter Mutations In Thyroid Carcinomasmentioning

confidence: 87%

“…A TERT copy number gain was described in familial PTC [14], but this finding was not confirmed in another series [55]. A recent study by Capezzone and colleagues reported telomerase activity in most sporadic and familial malignant thyroid tumours as well as in some adenomas [15]. Telomerase activity was not observed in hyperplastic nodules or in normal thyroid tissue from patients with sporadic PTC [15].…”

Section: Telomerase Promoter Mutations In Thyroid Carcinomasmentioning

confidence: 95%

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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“…Aneuploidy is a molecular feature that identifies genetic instability, and potentially, higher metastatic capacity, being commonly associated with worse disease prognosis (26,27). In two recent studies of familial PTC, although controversial (28), Capezzone et al observed shorter telomere length in the leukocytes, other non-neoplastic tissues and tumours in the familial cases when compared with patients with sporadic PTC or healthy subjects (29,30). The size reduction of these nucleoprotein complexes, which protect the ends of chromosomes from degradation and fusion, may induce chromosomal instability, and thus, aneuploidy in these familial tumours.…”

Section: Introductionmentioning

confidence: 99%

Familial vs sporadic papillary thyroid carcinoma: a matched-case comparative study showing similar clinical/prognostic behaviour

Pinto

Silva²,

Henrique

et al. 2014

European Journal of Endocrinology

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Objective: Familial non-medullary thyroid cancer has been proposed as an aggressive clinical entity. Our aim in this study is to investigate potential distinguishing features as well as the biological and clinical aggressiveness of familial vs sporadic papillary thyroid carcinoma (PTC). We assessed clinicopathological characteristics, outcome measures and DNA ploidy. Design: A matched-case comparative study. Methods: A series of patients with familial PTC (nZ107) and two subgroups, one with three or more affected elements (nZ32) and another including index cases only (nZ61), were compared with patients with sporadic PTC (nZ107), matched by age, gender, pTNM disease extension and approximate follow-up duration. Histological variant, extrathyroidal extension, vascular invasion, tumour multifocality and bilateral growth were evaluated. Ploidy pattern was analysed in available samples by DNA flow cytometry. The probabilities of disease-free survival (DFS) and overall survival (OS) were estimated according to the Kaplan-Meier (K-M) method. Results: No patient with familial PTC died of disease during follow-up (median, 72 months), contrarily to five patients (4.7%) (PZ0.06) with sporadic PTC (median, 90 months). There was a significantly higher tumour multifocality in familial PTC (index cases subgroup) vs sporadic PTC (PZ0.035), and a trend, in the familial PTC cohort with three or more affected elements, to show extrathyroidal extension (PZ0.054) more frequently. No difference was observed in DNA ploidy status. The K-M analyses showed no significant differences between both entities in relation to DFS or OS. Conclusion: Apart from multifocality, familial PTC appears to have similar clinical/prognostic behaviour when compared with sporadic forms of the disease.

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Telomere Length in Neoplastic and Nonneoplastic Tissues of Patients with Familial and Sporadic Papillary Thyroid Cancer

Abstract: Our results demonstrate that short telomeres are a consistent feature of PTC, which in familial cases, is not restricted to the tumor tissue. This finding suggests that FPTC has a distinct, heritable, genetic background.

Cited by 31 publications

References 17 publications

Frequency of TERT promoter mutations in human cancers

Frequency of TERT promoter mutations in human cancers

Telomerase promoter mutations in cancer: an emerging molecular biomarker?

Familial vs sporadic papillary thyroid carcinoma: a matched-case comparative study showing similar clinical/prognostic behaviour

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