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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

TCF12 mutation correlates with a higher necrotic and mitotic index.(a) Percentage of palisading necrosis in tumours with wild-type TCF12, all tumours mutated for TCF12 or only altered bHLH TCF12 mutants; *P=0.02, **P=0.004. (b) Mitotic index in TCF12 wild-type, TCF12-mutated and altered bHLH TCF12 mutants; *P=0.039, mean±s.e.m. CN, copy number; LOH, loss of heterozygosity; HPF, high-power field. The number of samples is indicated in parenthesis.
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f5: TCF12 mutation correlates with a higher necrotic and mitotic index.(a) Percentage of palisading necrosis in tumours with wild-type TCF12, all tumours mutated for TCF12 or only altered bHLH TCF12 mutants; *P=0.02, **P=0.004. (b) Mitotic index in TCF12 wild-type, TCF12-mutated and altered bHLH TCF12 mutants; *P=0.039, mean±s.e.m. CN, copy number; LOH, loss of heterozygosity; HPF, high-power field. The number of samples is indicated in parenthesis.

Mentions: We profiled the extent of necrosis, microvascular proliferation and the mitotic index available for TCF12 wild-type or mutated tumours. A significant increase in palisading necrosis (Fig. 5) as well as a trend towards a higher mitotic index was associated with TCF12 mutation, consistent with a more aggressive phenotype (Fig. 5). Intriguingly, tumours harbouring disruptive bHLH domain mutations exhibited the highest proportion of palisading necrosis and mitotic figures.


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)

TCF12 mutation correlates with a higher necrotic and mitotic index.(a) Percentage of palisading necrosis in tumours with wild-type TCF12, all tumours mutated for TCF12 or only altered bHLH TCF12 mutants; *P=0.02, **P=0.004. (b) Mitotic index in TCF12 wild-type, TCF12-mutated and altered bHLH TCF12 mutants; *P=0.039, mean±s.e.m. CN, copy number; LOH, loss of heterozygosity; HPF, high-power field. The number of samples is indicated in parenthesis.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f5: TCF12 mutation correlates with a higher necrotic and mitotic index.(a) Percentage of palisading necrosis in tumours with wild-type TCF12, all tumours mutated for TCF12 or only altered bHLH TCF12 mutants; *P=0.02, **P=0.004. (b) Mitotic index in TCF12 wild-type, TCF12-mutated and altered bHLH TCF12 mutants; *P=0.039, mean±s.e.m. CN, copy number; LOH, loss of heterozygosity; HPF, high-power field. The number of samples is indicated in parenthesis.
Mentions: We profiled the extent of necrosis, microvascular proliferation and the mitotic index available for TCF12 wild-type or mutated tumours. A significant increase in palisading necrosis (Fig. 5) as well as a trend towards a higher mitotic index was associated with TCF12 mutation, consistent with a more aggressive phenotype (Fig. 5). Intriguingly, tumours harbouring disruptive bHLH domain mutations exhibited the highest proportion of palisading necrosis and mitotic figures.

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