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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

Distribution of mutations in gliomasThe distribution of mutations in the TERT promoter, IDH1 and IDH2 (IDH) and deletions at 9p21 (CDKN2A/B), 1p and 19q. Mutations are indicated in different colours. TERT = telomerase reverse transcriptase; IDH1 = isocitrate dehydrogenase 1; IDH2 = isocitrate dehydrogenase 2; CDKN2A = cyclin-dependent kinase inhibitor 2A; CDKN2B = cyclin-dependent kinase inhibitor 2B; CDKN2C = cyclin-dependent kinase inhibitor 2C; chromosome arm 1p; chromosome arm 19q; wildtype = no mutation found within the investigated loci.
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Figure 1: Distribution of mutations in gliomasThe distribution of mutations in the TERT promoter, IDH1 and IDH2 (IDH) and deletions at 9p21 (CDKN2A/B), 1p and 19q. Mutations are indicated in different colours. TERT = telomerase reverse transcriptase; IDH1 = isocitrate dehydrogenase 1; IDH2 = isocitrate dehydrogenase 2; CDKN2A = cyclin-dependent kinase inhibitor 2A; CDKN2B = cyclin-dependent kinase inhibitor 2B; CDKN2C = cyclin-dependent kinase inhibitor 2C; chromosome arm 1p; chromosome arm 19q; wildtype = no mutation found within the investigated loci.

Mentions: Data on deletions at 1p and/or 19q were available for 259 gliomas. 74 tumors had deletions at chromosome arms 1p and/or 19q, of which 47 were co-deletions at both loci. The highest frequency of 1p/19q co-deletions was in oligodendrogliomas with 14/28 (56%), followed by oligoastrocytomas 19/47 (40%). The CDKN2C (p18INK4C) locus at chromosome 1p showed focal deletions in nine gliomas, of which eight were primary glioblastomas and one was a grade II astrocytoma. Of these nine, six tumors were also deleted at the CDKN2A/B and eight tumors carried TERT promoter mutations (Figure 1).


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)

Distribution of mutations in gliomasThe distribution of mutations in the TERT promoter, IDH1 and IDH2 (IDH) and deletions at 9p21 (CDKN2A/B), 1p and 19q. Mutations are indicated in different colours. TERT = telomerase reverse transcriptase; IDH1 = isocitrate dehydrogenase 1; IDH2 = isocitrate dehydrogenase 2; CDKN2A = cyclin-dependent kinase inhibitor 2A; CDKN2B = cyclin-dependent kinase inhibitor 2B; CDKN2C = cyclin-dependent kinase inhibitor 2C; chromosome arm 1p; chromosome arm 19q; wildtype = no mutation found within the investigated loci.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Distribution of mutations in gliomasThe distribution of mutations in the TERT promoter, IDH1 and IDH2 (IDH) and deletions at 9p21 (CDKN2A/B), 1p and 19q. Mutations are indicated in different colours. TERT = telomerase reverse transcriptase; IDH1 = isocitrate dehydrogenase 1; IDH2 = isocitrate dehydrogenase 2; CDKN2A = cyclin-dependent kinase inhibitor 2A; CDKN2B = cyclin-dependent kinase inhibitor 2B; CDKN2C = cyclin-dependent kinase inhibitor 2C; chromosome arm 1p; chromosome arm 19q; wildtype = no mutation found within the investigated loci.
Mentions: Data on deletions at 1p and/or 19q were available for 259 gliomas. 74 tumors had deletions at chromosome arms 1p and/or 19q, of which 47 were co-deletions at both loci. The highest frequency of 1p/19q co-deletions was in oligodendrogliomas with 14/28 (56%), followed by oligoastrocytomas 19/47 (40%). The CDKN2C (p18INK4C) locus at chromosome 1p showed focal deletions in nine gliomas, of which eight were primary glioblastomas and one was a grade II astrocytoma. Of these nine, six tumors were also deleted at the CDKN2A/B and eight tumors carried TERT promoter mutations (Figure 1).

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