TP53 and p53 statuses and their clinical impact in diffuse low grade gliomas

• Published in: Journal of neuro-oncology Vol. 118; no. 1; pp. 131 - 139
• Main Authors: Gillet, Emeline, Alentorn, Agusti, Doukouré, Brahima, Mundwiller, Emeline, van Thuij, Hinke, Reijneveld, Jaap C., Medina, José Alfonso Meza, Liou, Amélie, Marie, Yannick, Mokhtari, Karima, Hoang-Xuan, Khê, Sanson, Marc, Delattre, Jean-Yves, Idbaih, Ahmed
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01-05-2014; Springer Nature B.V
• Subjects: Adult; Brain Neoplasms - genetics; Brain Neoplasms - pathology; Chromosomes, Human, Pair 19; Clinical Study; Exons - genetics; Female; Glioma - genetics; Glioma - pathology; Humans; Male; Medicine; Medicine & Public Health; Middle Aged; Mutation - genetics; Neurology; Oncology; Retrospective Studies; ROC Curve; Survival Analysis; Tumor Suppressor Protein p53 - genetics; Prognosis; Low grade glioma; Mutation; Expression; TP53; P53
• ISSN: 0167-594X; 1573-7373
• DOI: 10.1007/s11060-014-1407-4

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.