New prognostic factor telomerase reverse transcriptase promotor mutation presents without MR imaging biomarkers in primary glioblastoma

Ersoy, Tunc Faik; Keil, Vera C.; Hadizadeh, Dariusch R.; Gielen, Gerrit H.; Fimmers, Rolf; Waha, Andreas; Heidenreich, Barbara; Kumar, Rajiv; Schild, Hans H.; Simon, Matthias

doi:10.1007/s00234-017-1920-1

Cited by 16 publications

(12 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Taken together with our findings, this supports the idea that in TERT‐wildtype tumors, mechanisms other than BBB disruption may play a larger role in tumor pathogenesis than in TERT‐mutated tumors. Few studies have examined the relationship between VASARI features and mutational status with only one other study specifically examining TERT, which found no significant difference in any of the VASARI features between TERT‐mutated and TERT‐wildtype groups . Differences in results may be secondary to interobserver variability.…”

Section: Discussionmentioning

confidence: 99%

“…Few studies have examined the relationship between VASARI features and mutational status with only one other study specifically examining TERT, which found no significant difference in any of the VASARI features between TERT-mutated and TERT-wildtype groups. 13 Differences in results may be secondary to interobserver variability.…”

Section: Discussionmentioning

confidence: 99%

“…There is a strong need for noninvasive in vivo imaging biomarkers to predict prognosis and to allow for a tailored treatment regimen in GBM. A recent study using the Visually Accessible Rembrandt Images (VASARI) feature set did not find significant correlation with TERT mutation status . Low apparent diffusion coefficient (ADC) values, reflecting hypercellularity, have been found to correlate with poor survival in malignant astrocytomas in a meta‐analysis comprising 181 patients .…”

Section: Introductionmentioning

confidence: 99%

“…A recent study using the Visually Accessible Rembrandt Images (VASARI) feature set 12 did not find significant correlation with TERT mutation status. 13 Low apparent diffusion coefficient (ADC) values, reflecting hypercellularity, have been found to correlate with poor survival in malignant astrocytomas in a meta-analysis comprising 181 patients. 14 However, ADC correlates of TERT promoter mutation status have not previously been reported.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

MRI Features Associated with TERT Promoter Mutation Status in Glioblastoma

Ivanidze

Lum

Pisapia

et al. 2019

Journal of Neuroimaging

View full text Add to dashboard Cite

BACKGROUND AND PURPOSE Telomerase reverse transcriptase (TERT) promoter mutations are associated with worse prognosis in glioblastoma. The purpose of this study was to evaluate whether TERT mutation status was associated with specific morphologic and quantitative imaging features. METHODS Twenty‐nine patients with isocitrate dehydrogenase 1/2‐wildtype glioblastoma (13 TERT‐wildtype, 16 TERT‐mutated), who underwent preoperative magnetic resonance (MR) imaging were included in this retrospective study. Qualitative imaging phenotypes were evaluated using the Visually Accessible Rembrandt Images (VASARIs) feature set. Histogram analysis of apparent diffusion coefficient (ADC) and dynamic contrast‐enhanced MR perfusion values were performed on enhancing tumor volumes‐of‐interest, and differences between TERT‐wildtype and TERT‐mutated tumors were assessed. RESULTS VASARI analysis demonstrated that the majority of morphologic features were not significantly different between TERT‐wildtype and TERT‐mutated tumors, although a higher proportion of TERT‐wildtype tumors featured nonenhancing tumor crossing midline (P = .014). TERT‐mutated tumors demonstrated lower median rate constant kep (.38 vs. .76, P = .03) and lower median volume transfer coefficient Ktrans (.13 vs. .31, P = .02). There was no significant difference in median plasma volume vp (P = .92) or ADC values (P = .66) between the two groups. We further found a significant interaction between median kep and Ktrans and TERT status, respectively, suggesting greater risk of death with increasing blood‐brain barrier dysfunction in TERT‐mutated but not in TERT‐wildtype tumors. CONCLUSION Our study demonstrates evidence of altered permeability metrics associated with TERT mutation in glioblastoma, laying the foundation for future prospective studies assessing implications for therapeutic management and clinical outcomes.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

MRI Features Associated with TERT Promoter Mutation Status in Glioblastoma

Ivanidze

Lum

Pisapia

et al. 2019

Journal of Neuroimaging

View full text Add to dashboard Cite

show abstract

“…In bladder cancer, besides being associated with an increased disease recurrence and poor patient outcome, the specificity of the TERT promoter mutations distinguishes histologically deceptive cancers from benign mimics 88,112 . In gliomas, the TERT promoter mutations associated with high disease grade, worst patient survival, and other markers follow histological classification into subgroups with distinct disease outcomes 75,[113][114][115][116][117][118][119] . An investigation based on editing out of the TERT promoter mutations showed that the local injection of adenine base editor fused to Campylobacter jejuni CRISPR-associated protein 9 inhibited the growth of gliomas harboring those alterations 120 .…”

Section: Impact Of Tert Promoter Mutationsmentioning

confidence: 99%

Occurrence, functionality, and abundance of theTERTpromoter mutations

Rachakonda

Hoheisel

Kumar

2021

Preprint

Self Cite

View full text Add to dashboard Cite

Telomere shortening at chromosomal ends due to the constraints of the DNA replication process acts as a tumor suppressor by restricting the replicative potential in primary cells. Cancers evade that limitation primarily through rejuvenation of telomerase via different mechanisms. Mutations within the promoter of the telomerase reverse transcriptase (TERT) gene define a definite method for the ribonucleic enzyme regeneration predominantly in cancers that arise from tissues with low rates of self-renewal. The promoter mutations cause a moderate surge in TERT transcription and telomerase rejuvenation to the levels sufficient to delay replicative senescence but not prevent bulk telomere shortening and genomic instability. Since the discovery, a staggering number of studies and publications have resolved the discrete aspects, effects, and clinical relevance of the TERT promoter mutations. Those noncoding alterations link the TERT transcription with oncogenic pathways, associate with markers of poor outcome, and define patients with reduced survivals in several cancers. In this review, we discuss the occurrence and impact of the promoter mutations and highlight the mechanism of TERT activation. We further deliberate on the foundational question of the abundance of the TERT promoter mutations and a general dearth of functional mutations within noncoding sequences as evident from pan-cancer analysis of the whole-genomes. We posit that the favorable genomic constellation within the TERT promoter may be less than a common occurrence in other noncoding functional elements and the evolutionary constraints limit the functional fraction within the human genome, hence the lack of abundant mutations outside the coding sequences.

show abstract

Occurrence, functionality and abundance of the TERT promoter mutations

Rachakonda

Hoheisel

Kumar

2021

Intl Journal of Cancer

Self Cite

View full text Add to dashboard Cite

Telomere shortening at chromosomal ends due to the constraints of the DNA replication process acts as a tumor suppressor by restricting the replicative potential in primary cells. Cancers evade that limitation primarily through the reactivation of telomerase via different mechanisms. Mutations within the promoter of the telomerase reverse transcriptase (TERT) gene represent a definite mechanism for the ribonucleic enzyme regeneration predominantly in cancers that arise from tissues with low rates of self-renewal. The promoter mutations cause a moderate increase in TERT transcription and consequent telomerase upregulation to the levels sufficient to delay replicative senescence but not prevent bulk telomere shortening and genomic instability. Since the discovery, a staggering number of studies have resolved the discrete aspects, effects and clinical relevance of the TERT promoter mutations. The promoter mutations link transcription of TERT with oncogenic pathways, associate with markers of poor outcome and define patients with reduced survivals in several cancers. In this review, we discuss the occurrence and impact of the promoter mutations and highlight the mechanism of TERT activation. We further deliberate on the foundational question of the abundance of the TERT promoter mutations and a general dearth of functional mutations within noncoding sequences, as evident from pan-cancer analysis of the whole-genomes. We posit that the favorable genomic constellation within the TERT promoter may be less than a common occurrence in other noncoding functional elements. Besides, the evolutionary constraints limit the functional fraction within the human genome, hence the lack of abundant mutations outside the coding sequences.

show abstract

New prognostic factor telomerase reverse transcriptase promotor mutation presents without MR imaging biomarkers in primary glioblastoma

Abstract: Imaging biomarkers for prediction of TERT mutation status remain weak and cannot be derived from the VASARI protocol. Tumor-associated seizures are less common in TERT mutated glioblastomas.

Cited by 16 publications

References 46 publications

MRI Features Associated with TERT Promoter Mutation Status in Glioblastoma

MRI Features Associated with TERT Promoter Mutation Status in Glioblastoma

Occurrence, functionality, and abundance of theTERTpromoter mutations

Occurrence, functionality and abundance of the TERT promoter mutations

Contact Info

Product

Resources

About