Limits...
TCF12 is mutated in anaplastic oligodendroglioma.

Labreche K, Simeonova I, Kamoun A, Gleize V, Chubb D, Letouzé E, Riazalhosseini Y, Dobbins SE, Elarouci N, Ducray F, de Reyniès A, Zelenika D, Wardell CP, Frampton M, Saulnier O, Pastinen T, Hallout S, Figarella-Branger D, Dehais C, Idbaih A, Mokhtari K, Delattre JY, Huillard E, Mark Lathrop G, Sanson M, Houlston RS, POLA Netwo - Nat Commun (2015)

Bottom Line: Overall, 7.5% of AO are mutated for TCF12, which encodes an oligodendrocyte-related transcription factor.Eighty percent of TCF12 mutations identified were in either the bHLH domain, which is important for TCF12 function as a transcription factor, or were frameshift mutations leading to TCF12 truncated for this domain.Our analysis provides further insights into the unique and shared pathways driving AO.

View Article: PubMed Central - PubMed

Affiliation: 1] Division of Genetics and Epidemiology, The Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK [2] Inserm, U 1127, ICM, F-75013 Paris, France [3] CNRS, UMR 7225, ICM, F-75013 Paris, France [4] Institut du Cerveau et de la Moelle épinière ICM, Paris 75013, France [5] Sorbonne Universités, UPMC Université Paris 06, UMR S 1127, F-75013 Paris, France.

ABSTRACT
Anaplastic oligodendroglioma (AO) are rare primary brain tumours that are generally incurable, with heterogeneous prognosis and few treatment targets identified. Most oligodendrogliomas have chromosomes 1p/19q co-deletion and an IDH mutation. Here we analysed 51 AO by whole-exome sequencing, identifying previously reported frequent somatic mutations in CIC and FUBP1. We also identified recurrent mutations in TCF12 and in an additional series of 83 AO. Overall, 7.5% of AO are mutated for TCF12, which encodes an oligodendrocyte-related transcription factor. Eighty percent of TCF12 mutations identified were in either the bHLH domain, which is important for TCF12 function as a transcription factor, or were frameshift mutations leading to TCF12 truncated for this domain. We show that these mutations compromise TCF12 transcriptional activity and are associated with a more aggressive tumour type. Our analysis provides further insights into the unique and shared pathways driving AO.

No MeSH data available.


Related in: MedlinePlus

FM-biased genes and gene modules in AO identified by Oncodrive-fm using data from this study and tumours profiled by TCGA.Heatmap shows tumours in columns and genes in rows, the colour reflecting the MutationAssessor (MA) scores of somatic mutations. FM ext. qv, corrected P values of the FM bias analysis using the external  distribution.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4490400&req=5

f2: FM-biased genes and gene modules in AO identified by Oncodrive-fm using data from this study and tumours profiled by TCGA.Heatmap shows tumours in columns and genes in rows, the colour reflecting the MutationAssessor (MA) scores of somatic mutations. FM ext. qv, corrected P values of the FM bias analysis using the external distribution.

Mentions: A bias towards variants with functional impact (FM) is a feature of cancer drivers14. To increase our ability to identify cancer drivers and delineate associated oncogenic pathways for AO, we incorporated mutation data from multiple tumour types using Oncodrive-fm14 implemented within the IntOGen-mutations platform15 (Fig. 2). The most recurrently mutated genes according to MutSig were also detected by Oncodrive-fm as significantly mutated (Q-value<0.05). Oncodrive-fm also identified a number of other important mutated genes (that is, displaying high FM bias) including SETD2, NOTCH2, RBPJ, ARID1A, ARID1B, HDAC2 and SMARCA4 (Fig. 2).


TCF12 is mutated in anaplastic oligodendroglioma.

Labreche K, Simeonova I, Kamoun A, Gleize V, Chubb D, Letouzé E, Riazalhosseini Y, Dobbins SE, Elarouci N, Ducray F, de Reyniès A, Zelenika D, Wardell CP, Frampton M, Saulnier O, Pastinen T, Hallout S, Figarella-Branger D, Dehais C, Idbaih A, Mokhtari K, Delattre JY, Huillard E, Mark Lathrop G, Sanson M, Houlston RS, POLA Netwo - Nat Commun (2015)

FM-biased genes and gene modules in AO identified by Oncodrive-fm using data from this study and tumours profiled by TCGA.Heatmap shows tumours in columns and genes in rows, the colour reflecting the MutationAssessor (MA) scores of somatic mutations. FM ext. qv, corrected P values of the FM bias analysis using the external  distribution.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4490400&req=5

f2: FM-biased genes and gene modules in AO identified by Oncodrive-fm using data from this study and tumours profiled by TCGA.Heatmap shows tumours in columns and genes in rows, the colour reflecting the MutationAssessor (MA) scores of somatic mutations. FM ext. qv, corrected P values of the FM bias analysis using the external distribution.
Mentions: A bias towards variants with functional impact (FM) is a feature of cancer drivers14. To increase our ability to identify cancer drivers and delineate associated oncogenic pathways for AO, we incorporated mutation data from multiple tumour types using Oncodrive-fm14 implemented within the IntOGen-mutations platform15 (Fig. 2). The most recurrently mutated genes according to MutSig were also detected by Oncodrive-fm as significantly mutated (Q-value<0.05). Oncodrive-fm also identified a number of other important mutated genes (that is, displaying high FM bias) including SETD2, NOTCH2, RBPJ, ARID1A, ARID1B, HDAC2 and SMARCA4 (Fig. 2).

Bottom Line: Overall, 7.5% of AO are mutated for TCF12, which encodes an oligodendrocyte-related transcription factor.Eighty percent of TCF12 mutations identified were in either the bHLH domain, which is important for TCF12 function as a transcription factor, or were frameshift mutations leading to TCF12 truncated for this domain.Our analysis provides further insights into the unique and shared pathways driving AO.

View Article: PubMed Central - PubMed

Affiliation: 1] Division of Genetics and Epidemiology, The Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK [2] Inserm, U 1127, ICM, F-75013 Paris, France [3] CNRS, UMR 7225, ICM, F-75013 Paris, France [4] Institut du Cerveau et de la Moelle épinière ICM, Paris 75013, France [5] Sorbonne Universités, UPMC Université Paris 06, UMR S 1127, F-75013 Paris, France.

ABSTRACT
Anaplastic oligodendroglioma (AO) are rare primary brain tumours that are generally incurable, with heterogeneous prognosis and few treatment targets identified. Most oligodendrogliomas have chromosomes 1p/19q co-deletion and an IDH mutation. Here we analysed 51 AO by whole-exome sequencing, identifying previously reported frequent somatic mutations in CIC and FUBP1. We also identified recurrent mutations in TCF12 and in an additional series of 83 AO. Overall, 7.5% of AO are mutated for TCF12, which encodes an oligodendrocyte-related transcription factor. Eighty percent of TCF12 mutations identified were in either the bHLH domain, which is important for TCF12 function as a transcription factor, or were frameshift mutations leading to TCF12 truncated for this domain. We show that these mutations compromise TCF12 transcriptional activity and are associated with a more aggressive tumour type. Our analysis provides further insights into the unique and shared pathways driving AO.

No MeSH data available.


Related in: MedlinePlus