TERT promoter methylation and protein expression as predictive biomarkers for recurrence risk in patients with serous borderline ovarian tumours

Losi, Lorena; Botticelli, Laura; Garagnani, Lorenzo; Fabbiani, Luca; Panini, Rossana; Gallo, Graziana; Sabbatini, Roberto; Maiorana, Antonino; Benhattar, Jean

doi:10.1016/j.pathol.2020.07.010

Cited by 3 publications

(1 citation statement)

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“…Estrogen from the granulosa cell compartment could reach the epithelial cells, inducing telomerase activation and oncogenic transformation of the ovarian epithelium [124]. The levels of telomerase activity correlate with the severity and recurrence of ovarian cancers [125]. Recently, effective telomerase-molecular targeted therapy has been tested as an approach for the treatment of ovarian cancer [126].…”

Section: Discussionmentioning

confidence: 99%

Ovarian Telomerase and Female Fertility

Toupance

Fattet²,

Thornton

et al. 2021

Biomedicines

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Women’s fertility is characterized both quantitatively and qualitatively mainly by the pool of ovarian follicles. Monthly, gonadotropins cause an intense multiplication of granulosa cells surrounding the oocyte. This step of follicular development requires a high proliferation ability for these cells. Telomere length plays a crucial role in the mitotic index of human cells. Hence, disrupting telomere homeostasis could directly affect women’s fertility. Strongly expressed in ovaries, telomerase is the most effective factor to limit telomeric attrition and preserve ovarian reserve. Considering these facts, two situations of infertility could be correlated with the length of telomeres and ovarian telomerase activity: PolyCystic Ovary Syndrome (PCOS), which is associated with a high density of small antral follicles, and Premature Ovarian Failure (POF), which is associated with a premature decrease in ovarian reserve. Several authors have studied this topic, expecting to find long telomeres and strong telomerase activity in PCOS and short telomeres and low telomerase activity in POF patients. Although the results of these studies are contradictory, telomere length and the ovarian telomerase impact in women’s fertility disorders appear obvious. In this context, our research perspectives aimed to explore the stimulation of ovarian telomerase to limit the decrease in the follicular pool while avoiding an increase in cancer risk.

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Section: Discussionmentioning

confidence: 99%

Ovarian Telomerase and Female Fertility

Toupance

Fattet²,

Thornton

et al. 2021

Biomedicines

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Gene Expression Profiles of AHNAK2, DCSTAMP, FN1, and TERT Correlate With Mutational Status and Recurrence in Papillary Thyroid Carcinoma

Staubitz‐Vernazza,

Müller,

Heymans

et al. 2024

Genes Chromosomes & Cancer

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Papillary thyroid carcinoma (PTC), the most common malignancy of follicular cell derivation, is generally associated with good prognosis. Nevertheless, it is important to identify patients with aggressive PTCs and unfavorable outcome. Molecular markers such as BRAFV600E mutation and TERT promoter mutations have been proposed for risk stratification. While TERT promoter mutations have been frequently associated with aggressive PTCs, the association of BRAFV600E mutation with increased recurrence and mortality is less clear and has been controversially discussed. The aim of the present study was to analyze whether differentially expressed genes can predict BRAFV600E mutations as well as TERT promoter mutations in PTCs. RNA sequencing identified a large number of differentially expressed genes between BRAFV600E and BRAFwildtype PTCs. Of those, AHNAK2, DCSTAMP, and FN1 could be confirmed in a larger cohort (n = 91) to be significantly upregulated in BRAFV600E mutant PTCs using quantitative RT‐PCR. Moreover, individual PTC expression values of DCSTAMP and FN1 were able to predict the BRAFV600E mutation status with high sensitivity and specificity. The expression of TERT was detected in all PTCs harboring TERT promoter mutations and in 19% of PTCs without TERT promoter mutations. Tumors with both TERT expression and TERT promoter mutations were particularly associated with aggressive clinicopathological features and a shorter recurrence‐free survival. Altogether, it will be interesting to explore the biological function of AHNAK2, DCSTAMP, and FN1 in PTC in more detail. The analysis of their expression patterns could allow the characterization of PTC subtypes and thus enabling a more individualized surgical and medical treatment.

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