AI Article Synopsis

  • The TERT promoter (TERTp) mutation is the most common mutation in glioblastomas, leading to increased telomerase activity, while the rs2853669 variant affects a different Ets/TCF binding site without impacting overall survival.
  • A study of 651 glioblastoma patients found that the TERTp mutation was independent of the rs2853669 genotype, with the mutation linked to older age and specific chromosomal abnormalities.
  • The research highlights the complex relationship between TERTp mutation, EGFR amplification, and prognosis, confirming that EGFR's impact on outcomes varies based on TERTp status.

Article Abstract

TERT promoter (TERTp) mutation is the most common mutation in glioblastomas. It creates a putative binding site for Ets/TCF transcription factors, enhancing telomerase expression and activity, whereas the rs2853669 variant disrupts another Ets/TCF binding. We explore here the interaction between these two alterations, tumor genomic profile and the impact on prognosis. The TERTp and rs2853669 statuses were determined and confronted with the outcome and molecular profile, i.e., loss of chromosome 10q, CDKN2A deletion, IDH mutation, EGFR amplification, MGMT promoter methylation. 651 glioblastomas were selected (sex ratio = 1.35, median age 60.4 years, median survival 13.5 months). The TERTp mutation found in 481 patients (74 %) was independent from rs2853669 genotypes. TERTp mutation, but not rs2853669 status, was associated with older age (61.4 vs. 52.8 years). rs2853669 status had no impact on overall survival (OS) either in mutated TERTp or wild-type TERTp. Neither rs2736100 (TERT, 5q15.33) nor rs192011116 (TERC, 3q26.2) status had any impact on survival or showed any association with a TERTp mutation. The TERTp mutation was associated with EGFR amplification chromosome 10q loss, CDKN2A deletion and IDH wt. EGFR amplification was associated with a better outcome in TERTp mutated GBM, and a worse outcome in TERTp WT. This study-the largest analyzing the TERTp mutation and the rs2853669 polymorphism-fails to find any prognostic impact of rs2853669. It confirms the dual prognostic impact of EGFR amplification depending on TERTp status.

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11060-015-1999-3DOI Listing

Publication Analysis

Top Keywords

tertp mutation
24
egfr amplification
16
prognostic impact
12
tertp
12
tert promoter
8
rs2853669
8
mutation
8
chromosome 10q
8
cdkn2a deletion
8
deletion idh
8

Similar Publications

Gliomas are a heterogeneous group of brain tumors, among which the most aggressive subtype is glioblastoma, accounting for 60% of cases in adults. Available systemic treatment options are few and ineffective, so new approaches to therapies for glioblastoma are in high demand. In total, 131 patients with diffuse glioma were studied.

View Article and Find Full Text PDF

Choroid plexus tumors in adults: a retrospective mono-institutional study.

Neurol Sci

December 2024

Neuroncology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.

Purpose: Choroid plexus tumors (CPT) are rare entities, and even rarer in adulthood.

Methods: A retrospective consecutive series of 24 adult CPT patients was reviewed.

Results: We described 24 adult CPTs.

View Article and Find Full Text PDF

Background: The screening of TERT promoter () mutations is essential in cancer research and diagnostics, due to its prevalence in tumours associated with low self-renewal rates. TERTmonitor is a diagnosis kit primarily designed for real-time qPCR qualitative detection of -124C>T and -146C>T mutations, which are highly prevalent in several malignancies, particularly in bladder carcinoma.

Objective: This study aims to investigate TERTmonitor performance in droplet digital PCR (ddPCR) in urine samples from bladder cancer patients.

View Article and Find Full Text PDF

Mechanistic basis of atypical TERT promoter mutations.

Nat Commun

November 2024

Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

Non-coding mutations in the TERT promoter (TERTp), typically at one of two bases -124 and -146 bp upstream of the start codon, are among the most prevalent driver mutations in human cancer. Several additional recurrent TERTp mutations have been reported but their functions and origins remain largely unexplained. Here, we show that atypical TERTp mutations arise secondary to canonical TERTp mutations in a two-step process.

View Article and Find Full Text PDF

The coexistence of v-Raf murine sarcoma viral oncogene homolog B1 () and telomere reverse transcriptase promoter (-p) mutations is considerably associated with aggressiveness and poor prognosis in papillary thyroid carcinoma (PTC). However, the association between gross findings and genetic alterations in PTC remains unknown. We aimed to investigate the association between clinicopathologic features, including macroscopic features, and the coexistent and -p mutations in patients with PTC.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!

A PHP Error was encountered

Severity: Notice

Message: fwrite(): Write of 34 bytes failed with errno=28 No space left on device

Filename: drivers/Session_files_driver.php

Line Number: 272

Backtrace:

A PHP Error was encountered

Severity: Warning

Message: session_write_close(): Failed to write session data using user defined save handler. (session.save_path: /var/lib/php/sessions)

Filename: Unknown

Line Number: 0

Backtrace: