Three-Dimensional Telomere Dynamics in Follicular Thyroid Cancer

Wark, Landon; Danescu, Adrian; Natarajan, Suchitra; Zhu, Xuguang; Cheng, Sheue-yann; Hombach‐Klonisch, Sabine; Mai, Sabine; Klonisch, Thomas

doi:10.1089/thy.2013.0118

Cited by 8 publications

(4 citation statements)

References 62 publications

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“…Telomere remodeling is a feature of cancer cells [38] and may identify tumor subgroups [39,40]. On the other hand, alterations in the telomere 3D profile have been reported in a murine model of thyroid tumors [41]. Recurrent somatic mutations in the promoter of TERT, the catalytic subunit of the enzyme telomerase, has been reported in PTC [42], often in concomitance with mutated BRAF [43].…”

Section: Discussionmentioning

confidence: 99%

Genetic Heterogeneity of HER2 Amplification and Telomere Shortening in Papillary Thyroid Carcinoma

Caria

Cantara

Frau

et al. 2016

IJMS

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Extensive research is dedicated to understanding if sporadic and familial papillary thyroid carcinoma are distinct biological entities. We have previously demonstrated that familial papillary thyroid cancer (fPTC) cells exhibit short relative telomere length (RTL) in both blood and tissues and that these features may be associated with chromosome instability. Here, we investigated the frequency of HER2 (Human Epidermal Growth Factor Receptor 2) amplification, and other recently reported genetic alterations in sporadic PTC (sPTC) and fPTC, and assessed correlations with RTL and BRAF mutational status. We analyzed HER2 gene amplification and the integrity of ALK, ETV6, RET, and BRAF genes by fluorescence in situ hybridization in isolated nuclei and paraffin-embedded formalin-fixed sections of 13 fPTC and 18 sPTC patients. We analyzed BRAFV600E mutation and RTL by qRT-PCR. Significant HER2 amplification (p = 0.0076), which was restricted to scattered groups of cells, was found in fPTC samples. HER2 amplification in fPTCs was invariably associated with BRAFV600E mutation. RTL was shorter in fPTCs than sPTCs (p < 0.001). No rearrangements of other tested genes were observed. These findings suggest that the association of HER2 amplification with BRAFV600E mutation and telomere shortening may represent a marker of tumor aggressiveness, and, in refractory thyroid cancer, may warrant exploration as a site for targeted therapy.

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Section: Discussionmentioning

confidence: 99%

Genetic Heterogeneity of HER2 Amplification and Telomere Shortening in Papillary Thyroid Carcinoma

Caria

Cantara

Frau

et al. 2016

IJMS

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“…Our previous data have shown altered 3D telomeric organization in cervical cancer, glioblastoma, head and neck cancer, and thyroid cancer. 10,12,16,19,26 Thus, we investigated whether there was a difference in 3D nuclear telomere architecture between normal esophageal epithelial cells and esophageal cancer cells and also between young-and old-aged patients.…”

Section: Discussionmentioning

confidence: 99%

Three-dimensional telomere architecture of esophageal squamous cell carcinoma: comparison of tumor and normal epithelial cells

Sunpaweravong

Sathitruangsak

et al. 2015

Dis Esophagus

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Telomeres are repetitive nucleotide sequences (TTAGGG)n located at the ends of chromosomes that function to preserve chromosomal integrity and prevent terminal end-to-end fusions. Telomere loss or dysfunction results in breakage-bridge-fusion cycles, aneuploidy, gene amplification and chromosomal rearrangements, which can lead to genomic instability and promote carcinogenesis. Evaluating the hypothesis that changes in telomeres contribute to the development of esophageal squamous cell carcinoma (ESCC) and to determine whether there are differences between young and old patients, we compared the three-dimensional (3D) nuclear telomere architecture in ESCC tumor cells with that of normal epithelial cells obtained from the same patient. Patients were equally divided by age into two groups, one comprising those less than 45 years of age and the other consisting of those over 80 years of age. Tumor and normal epithelial cells located at least 10 cm from the border of the tumor were biopsied in ESCC patients. Hematoxylin and eosin staining was performed for each sample to confirm and identify the cancer and normal epithelial cells. This study was based on quantitative 3D fluorescence in situ hybridization (Q-FISH), 3D imaging and 3D analysis of paraffin-embedded slides. The 3D telomere architecture data were computer analyzed using 100 nuclei per slide. The following were the main parameters compared: the number of signals (number of telomeres), signal intensity (telomere length), number of telomere aggregates, and nuclear volume. Tumor and normal epithelial samples from 16 patients were compared. The normal epithelial cells had more telomere signals and higher intensities than the tumor cells, with P-values of P < 0.0001 and P = 0.0078, respectively. There were no statistically significant differences in the numbers of telomere aggregates or the nuclear volumes between the tumor and normal epithelial cells. Secondary analyses examined the effects of age on 3D telomere architecture and found no statistically significant differences in any parameter tested between the young and old patients in either the tumor or epithelial cells. The 3D nuclear telomeric signature was able to detect differences in telomere architecture between the ESCC and normal epithelial tissues. However, there were no differences observed between the young and old patients.

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“…The three-dimensional (3D) telomeres analysis using TeloView® technology has been shown to be a reliable tool for the assessment of genomic instability in several cancers including hematological disorders (35,36,37,38,39,40) and carcinomas (41,42,43,44). In particular, TeloView® analysis has been extensively used in a number of published studies addressing critical clinical questions regarding the biology of cHL (27,29,31,45,46,47).…”

Section: Introductionmentioning

confidence: 99%

Analysis by TeloView® Technology Predicts the Response of Hodgkin’s Lymphoma to first line ABVD Therapy

Knecht,

Johnson,

Bienz

et al. 2024

Preprint

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Classic Hodgkin’s lymphoma (cHL) is a curable cancer with disease-free survival rate of over 10 years. Over 80% of diagnosed patients respond favorably to first line chemotherapy. However, 15-20% of patients experience refractory or early relapsed disease. To date, the identification of such patients is still not possible using traditional clinical risk factors. The three-dimensional (3D) telomere analysis has been shown to be a reliable structural biomarker to quantify genomic instability, inform on disease progression, and predict patients’ response to therapy in several cancers, particularly hematological disorders. The 3D telomere analysis previously also elucidated biological mechanisms related to cHL disease progression. Here we report results of a multicenter retrospective clinical study including 156 cHL patients. We used the cohort data as a training dataset and identified significant 3D telomere parameters suitable to predict individual patient outcome at point of diagnosis. Multivariate analysis allowed for developing a predictive model using four telomeric parameters as predictors, including the proportion of t-stumps (very short telomeres). The percentage of t-stumps was the most prominent predictor to identify refractory/relapsing cHL prior to the initiation of ABVD therapy. The model characteristics include AUC of 0.83 in ROC analysis, sensitivity, and specificity of 0.8 and 0.75 respectively.

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Three-Dimensional Telomere Dynamics in Follicular Thyroid Cancer

Cited by 8 publications

References 62 publications

Genetic Heterogeneity of HER2 Amplification and Telomere Shortening in Papillary Thyroid Carcinoma

Genetic Heterogeneity of HER2 Amplification and Telomere Shortening in Papillary Thyroid Carcinoma

Three-dimensional telomere architecture of esophageal squamous cell carcinoma: comparison of tumor and normal epithelial cells

Analysis by TeloView® Technology Predicts the Response of Hodgkin’s Lymphoma to first line ABVD Therapy

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