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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

Telomere lengths in glioma tumorsRelative telomere length in gliomas without and with TERT promoter mutations. Experiments were carried out in triplicate and box plots represent mean ± s.e.m. P-values were determined by t-test.
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Figure 3: Telomere lengths in glioma tumorsRelative telomere length in gliomas without and with TERT promoter mutations. Experiments were carried out in triplicate and box plots represent mean ± s.e.m. P-values were determined by t-test.

Mentions: Results from measurement of relative telomere length were available for 285 gliomas of which 190 were with and 95 were without TERT promoter mutations. Relative telomere length ranged between 0.01 and 4.24 with a median value of 0.53. Tumors carrying TERT promoter mutations had shorter telomeres (median 0.44) compared to tumors without mutations (median 0.94, P < 0.0001, t-test; Figure 3). Stratification of the data according to age showed that the differences in relative telomere lengths in tumors with TERT promoter mutations was statistically significant in patients with age ≤ 52 years at diagnosis (P < 0.0001, t-test; Supplementary Figure 1) but not in patients with age > 52 (P = 0.3). Stratification of the data according to the combined IDH and TERT promoter status revealed that only in the two groups that carry TERT promoter mutations (TERT promoter mutated and either IDH mutated or wildtype) telomere lengths is statistically significant shorter than in tumors that carry neither of the mutations (Supplementary Figure 2).


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)

Telomere lengths in glioma tumorsRelative telomere length in gliomas without and with TERT promoter mutations. Experiments were carried out in triplicate and box plots represent mean ± s.e.m. P-values were determined by t-test.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Telomere lengths in glioma tumorsRelative telomere length in gliomas without and with TERT promoter mutations. Experiments were carried out in triplicate and box plots represent mean ± s.e.m. P-values were determined by t-test.
Mentions: Results from measurement of relative telomere length were available for 285 gliomas of which 190 were with and 95 were without TERT promoter mutations. Relative telomere length ranged between 0.01 and 4.24 with a median value of 0.53. Tumors carrying TERT promoter mutations had shorter telomeres (median 0.44) compared to tumors without mutations (median 0.94, P < 0.0001, t-test; Figure 3). Stratification of the data according to age showed that the differences in relative telomere lengths in tumors with TERT promoter mutations was statistically significant in patients with age ≤ 52 years at diagnosis (P < 0.0001, t-test; Supplementary Figure 1) but not in patients with age > 52 (P = 0.3). Stratification of the data according to the combined IDH and TERT promoter status revealed that only in the two groups that carry TERT promoter mutations (TERT promoter mutated and either IDH mutated or wildtype) telomere lengths is statistically significant shorter than in tumors that carry neither of the mutations (Supplementary Figure 2).

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