Abstract
TP53 is a pivotal gene frequently mutated in diffuse gliomas and particularly in astrocytic tumors. The majority of studies dedicated to TP53 in gliomas were focused on mutational hotspots located in exons 5–8. Recent studies have suggested that TP53 is also mutated outside the classic mutational hotspots reported in gliomas. Therefore, we have sequenced all TP53 coding exons in a retrospective series of 61 low grade gliomas (LGG) using high throughput sequencing technology. In addition, TP53 mutational status was correlated with: (i) p53 expression, (ii) tumor type, (iii) chromosome arms 1p/19q status and (iv) clinical features of patients. The cohort included 32 oligodendrogliomas (O), 21 oligoastrocytomas (M) and 8 astrocytomas (A). TP53 mutation was detected in 52.4 % (32/61) of tumors (34 % of O, 71.4 % of M and 75 % of A). All mutations (38 mutations in 32 samples) were detected in exons 4, 5, 6, 7, 8 and 10. Missense and non-missense mutations, including seven novel mutations, were detected in 42.6 and 9.8 % of tumors respectively. TP53 mutations were almost mutually exclusive with 1p/19q co-deletion and were associated with: (i) astrocytic phenotype, (ii) younger age, (iii) p53 expression. Using a threshold of 10 % p53-positive tumor cells, p53 expression is an interesting surrogate marker for missense TP53 mutations (Se = 92 %; Sp = 79.4 %) but not for non-missense mutation (18.4 % of mutations). TP53 and p53 statuses were not prognostic in LGG. In conclusion, we have identified novel TP53 mutations in LGG. TP53 mutations outside exons 4–8 are rare. Although it remains imperfect, p53 expression with a threshold of 10 % is a good surrogate marker for missense TP53 mutations and appears helpful in the setting of LGG phenotype diagnosis.
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Acknowledgments
The research leading to these results received funding from the program “Investissements d’avenir” ANR-10-IAIHU-06. AA has been granted by “Obra Social la Caixa” and ARTC (Association pour la Recherche sur les Tumeurs Cérébrales).
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Gillet, E., Alentorn, A., Doukouré, B. et al. TP53 and p53 statuses and their clinical impact in diffuse low grade gliomas. J Neurooncol 118, 131–139 (2014). https://doi.org/10.1007/s11060-014-1407-4
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DOI: https://doi.org/10.1007/s11060-014-1407-4