Elevated levels of telomerase activity in malignant pheochromocytoma

Kubota, Yōko; Nakada, Teruhiro; Sasagawa, Isoji; Yanai, Hiroshi; Ito, Kikukatsu

doi:10.1002/(sici)1097-0142(19980101)82:1<176::aid-cncr22>3.0.co;2-z

Cited by 58 publications

(17 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Early studies reported telomerase overexpression in malignant pheochromocytomas (19)(20)(21)(22)(23), whereas TERT promoter mutations (24,25) and hypermethylation (26) were recently found in a few SDHx-deficient paragangliomas. The phenotypic assignment of ALT based on telomeric analysis of histological preparations remains limited to 2 discrepant studies reporting a prevalence of 4% (27) and 27% (28) of 75 and 22 PPGLs, respectively.…”

Section: Introductionmentioning

confidence: 99%

Telomerase Activation and ATRX Mutations Are Independent Risk Factors for Metastatic Pheochromocytoma and Paraganglioma

Job

Drašković

Burnichon

et al. 2019

Clinical Cancer Research

100

View full text Add to dashboard Cite

Purpose: Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors. Whereas most PPGLs are benign, up to 20% may become metastatic with SDHB-and FH-mutated tumors showing the higher risk. We aimed at determining the contribution of immortalization mechanisms to metastatic progression.Experimental Design: Immortalization mechanisms were investigated in 200 tumors. To identify telomerase (þ) tumors, we analyzed genomic alterations leading to transcriptional activation of TERT comprising promoter mutations, hypermethylation and gain copy number. To identify tumors that activated the alternative lengthening of telomere (ALT) mechanism, we combined analyses of telomere length by slot blot, telomere heterogeneity by telomere FISH, and ATRX mutations by next-generation sequencing. Univariate/ multivariate and metastasis-free survival (MFS) and overall survival (OS) analyses were carried out for assessment of risk factors and clinical outcomes.Results: Only 37 of 200 (18.5%) tumors achieved immortalization. Telomerase activation occurred in 12 metastatic tumors and was prevalent in SDHB-mutated paragangliomas (P ¼ 2.42eÀ09). ALT features were present in 25 tumors, mostly pheochromocytomas, regardless of metastatic status or molecular group (P ¼ 0.169), yet ATRX mutations were found preferentially in SDHB/FH-mutated metastatic tumors (P ¼ 0.0014). Telomerase activation and ATRX mutations were independent factors of poor prognosis: MFS (hazard ratio, 48.2 and 33.1; P ¼ 6.50EÀ07 and 1.90EÀ07, respectively); OS (hazard ratio, 97.4 and 44.1; P ¼ 4.30EÀ03 and 2.00EÀ03, respectively) and were associated with worse MFS and OS (log-rank tests P < 0.0001).Conclusions: Assessment of telomerase activation and ATRX mutations could be used to identify metastatic PPGLs, particularly in tumors at high risk of progression.

show abstract

Section: Introductionmentioning

confidence: 99%

Telomerase Activation and ATRX Mutations Are Independent Risk Factors for Metastatic Pheochromocytoma and Paraganglioma

Job

Drašković

Burnichon

et al. 2019

Clinical Cancer Research

100

View full text Add to dashboard Cite

show abstract

“…Recently, a relatively reliable prediction of the malignant behavior of the pheochromocytoma has been presented. 6,7 However, the number of patients examined is not enough to draw a definite conclusion. Only careful follow up will give an answer as to whether this case is another primary paraganglioma in a setting of multiplicity or a metastatic one.…”

Section: Discussionmentioning

confidence: 99%

Ectopic pheochromocytoma arising in the spermatic cord 5 years after removal of bilateral carotid body tumors and adrenal pheochromocytomas

et al. 2000

View full text Add to dashboard Cite

show abstract

“…In contrast, the normal adrenal medullae or the benign pheochromocytomas showed no telomerase activity. 47 Telomerase is a ribonucleoprotein complex including the telomerase RNA component, the telomeraseassociated protein (TP1), the telomerase catalytic subunit (hTERT) and the heat shock protein 90 (HSP90). In one study, the telomerase RNA component was found in 100% of malignant (9/9) and in 46% (13/28) of benign pheochromacytomas; 100% of malignant (9/9), but only 7% of benign (2/28) pheochromacytomas expressed hTERT; and HSP90 was increased in malignant pheochromacytomas, expressed at a lower level in benign pheochromacytomas.…”

Section: Molecular Markers Studiesmentioning

confidence: 99%

Development of differential diagnosis for benign and malignant pheochromocytomas

Gao¹,

Kong²,

Zhang³

2008

Int J of Urology

View full text Add to dashboard Cite

Unlike common malignant tumors, malignant pheochromocytomas cannot be definitely diagnosed using histological features. This unique nature of pheochromocytomas provides a valuable model that may promote the investigation of the mechanism of other common malignant tumors where similar frameworks are not available. Studies on malignant pheochromocytomas should benefit not only the individuals with pheochromocytomas but those with other tumors. A review on the development of differentiating diagnosis between malignant and benign pheochromocytomas in imaging studies, biological fluid examinations, pathological examinations, molecular markers and genome studies, was updated in the hopes of guiding the next studies of pheochromcytomas.

show abstract

Elevated levels of telomerase activity in malignant pheochromocytoma

Abstract: The expression of telomerase activity in pheochromocytoma clearly suggests the malignant behavior of the component cells. Analysis of telomerase activity appears to be a powerful tool for the diagnosis of malignant pheochromocytoma.

Cited by 58 publications

References 18 publications

Telomerase Activation and ATRX Mutations Are Independent Risk Factors for Metastatic Pheochromocytoma and Paraganglioma

Telomerase Activation and ATRX Mutations Are Independent Risk Factors for Metastatic Pheochromocytoma and Paraganglioma

Ectopic pheochromocytoma arising in the spermatic cord 5 years after removal of bilateral carotid body tumors and adrenal pheochromocytomas

Development of differential diagnosis for benign and malignant pheochromocytomas

Contact Info

Product

Resources

About