Limits...
TERT promoter mutations and telomere length in adult malignant gliomas and recurrences.

Heidenreich B, Rachakonda PS, Hosen I, Volz F, Hemminki K, Weyerbrock A, Kumar R - Oncotarget (2015)

Bottom Line: Tumors with TERT promoter mutations compared to those without showed increased TERT transcription; we also showed difference in the transcription levels due to the two main mutations.TERT promoter mutations in low grade gliomas associated with reduced progression free survival (HR 10.2; 95% CI 1.9 - 55.9).While our data affirm the role of TERT promoter mutations in glial tumors, effects on transcription and telomere length emphasise the importance of telomere biology in disease genesis and outcome.

View Article: PubMed Central - PubMed

Affiliation: Division of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg 69120, Germany.

ABSTRACT
In this report on 303 gliomas we show the highest frequency of TERT promoter mutations in gliobastomas (80%) followed by oligodendrogliomas (70%) and astrocytomas (39%). We observed positive association between TERT promoter and IDH mutations in oligodendroglial tumors (OR = 26.3; 95% CI 2.5-250.2) and inverse association in primary glioblastomas (OR = 0.13; 95% CI 0.03-0.58). Tumors with TERT promoter mutations compared to those without showed increased TERT transcription; we also showed difference in the transcription levels due to the two main mutations. Tumors with TERT promoter mutations had shorter telomeres than those without. The patients with only TERT promoter mutations showed worst survival (median survival 14.6 months) and patients with both IDH and TERT promoter mutations showed best survival (246.5 months). In patients with astrocytoma, the TERT promoter mutations only associated with poor survival (P < 0.0001); IDH mutations and 1p/19q deletions associated with increased survival (P = 0.0004). TERT promoter mutations in low grade gliomas associated with reduced progression free survival (HR 10.2; 95% CI 1.9 - 55.9). While our data affirm the role of TERT promoter mutations in glial tumors, effects on transcription and telomere length emphasise the importance of telomere biology in disease genesis and outcome.

No MeSH data available.


Related in: MedlinePlus

Overall survival according to combined status of TERT promoter and IDH mutationsOverall survival in glioma patients where patient groups are defined by the mutational status of the TERT promoter and IDH1/IDH2.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4496380&req=5

Figure 5: Overall survival according to combined status of TERT promoter and IDH mutationsOverall survival in glioma patients where patient groups are defined by the mutational status of the TERT promoter and IDH1/IDH2.

Mentions: Stratification of patients based on the mutational status of the TERT promoter and IDH resulted in four groups with differing overall survival (P < 0.0001; Figure 5). The group with TERT promoter mutations and without IDH mutations showed worst overall survival (median survival 14.6 months), followed by the two groups without TERT promoter mutations that were either wildtype for IDH (median survival 28.5 months) or carried IDH mutations (median survival 110.6 months). Best overall survival was associated with the presence of both TERT promoter and IDH mutations (median survival 246.5 months), which resembles oligodendroglial progression. A multivariate model that included age, grade, treatment and loss of CDKN2A/B showed that the combined presence of TERT promoter and IDH mutations was the only independent factor (HR = 0.22; 95% HR CI 0.082 – 0.59; P = 0.03) (Supplementary Table 3). The adverse effect of only TERT promoter mutations was statistically significant in a model that did not include tumor grade and age (HR = 2.18; 95% HR CI 1.31 – 3.63; P = 0.003).


TERT promoter mutations and telomere length in adult malignant gliomas and recurrences.

Heidenreich B, Rachakonda PS, Hosen I, Volz F, Hemminki K, Weyerbrock A, Kumar R - Oncotarget (2015)

Overall survival according to combined status of TERT promoter and IDH mutationsOverall survival in glioma patients where patient groups are defined by the mutational status of the TERT promoter and IDH1/IDH2.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4496380&req=5

Figure 5: Overall survival according to combined status of TERT promoter and IDH mutationsOverall survival in glioma patients where patient groups are defined by the mutational status of the TERT promoter and IDH1/IDH2.
Mentions: Stratification of patients based on the mutational status of the TERT promoter and IDH resulted in four groups with differing overall survival (P < 0.0001; Figure 5). The group with TERT promoter mutations and without IDH mutations showed worst overall survival (median survival 14.6 months), followed by the two groups without TERT promoter mutations that were either wildtype for IDH (median survival 28.5 months) or carried IDH mutations (median survival 110.6 months). Best overall survival was associated with the presence of both TERT promoter and IDH mutations (median survival 246.5 months), which resembles oligodendroglial progression. A multivariate model that included age, grade, treatment and loss of CDKN2A/B showed that the combined presence of TERT promoter and IDH mutations was the only independent factor (HR = 0.22; 95% HR CI 0.082 – 0.59; P = 0.03) (Supplementary Table 3). The adverse effect of only TERT promoter mutations was statistically significant in a model that did not include tumor grade and age (HR = 2.18; 95% HR CI 1.31 – 3.63; P = 0.003).

Bottom Line: Tumors with TERT promoter mutations compared to those without showed increased TERT transcription; we also showed difference in the transcription levels due to the two main mutations.TERT promoter mutations in low grade gliomas associated with reduced progression free survival (HR 10.2; 95% CI 1.9 - 55.9).While our data affirm the role of TERT promoter mutations in glial tumors, effects on transcription and telomere length emphasise the importance of telomere biology in disease genesis and outcome.

View Article: PubMed Central - PubMed

Affiliation: Division of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg 69120, Germany.

ABSTRACT
In this report on 303 gliomas we show the highest frequency of TERT promoter mutations in gliobastomas (80%) followed by oligodendrogliomas (70%) and astrocytomas (39%). We observed positive association between TERT promoter and IDH mutations in oligodendroglial tumors (OR = 26.3; 95% CI 2.5-250.2) and inverse association in primary glioblastomas (OR = 0.13; 95% CI 0.03-0.58). Tumors with TERT promoter mutations compared to those without showed increased TERT transcription; we also showed difference in the transcription levels due to the two main mutations. Tumors with TERT promoter mutations had shorter telomeres than those without. The patients with only TERT promoter mutations showed worst survival (median survival 14.6 months) and patients with both IDH and TERT promoter mutations showed best survival (246.5 months). In patients with astrocytoma, the TERT promoter mutations only associated with poor survival (P < 0.0001); IDH mutations and 1p/19q deletions associated with increased survival (P = 0.0004). TERT promoter mutations in low grade gliomas associated with reduced progression free survival (HR 10.2; 95% CI 1.9 - 55.9). While our data affirm the role of TERT promoter mutations in glial tumors, effects on transcription and telomere length emphasise the importance of telomere biology in disease genesis and outcome.

No MeSH data available.


Related in: MedlinePlus