title: TP53 and p53 statuses and their clinical impact in diffuse low grade gliomas.
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.
authors.affiliation: Centre de Recherche de l'Institut du Cerveau et de la Moelle Epinière (CRICM), Université Pierre et Marie Curie-Paris 6, UMRS 975, Paris, France.
authors.forename: Emeline
authors.initials: E
authors.lastname: Gillet
authors.forename: Agusti
authors.initials: A
authors.lastname: Alentorn
authors.forename: Brahima
authors.initials: B
authors.lastname: Doukouré
authors.forename: Emeline
authors.initials: E
authors.lastname: Mundwiller
authors.forename: Hinke F
authors.initials: HF
authors.lastname: van Thuijl
authors.forename: Hinke
authors.initials: H
authors.lastname: van Thuij
authors.forename: Jaap C
authors.initials: JC
authors.lastname: Reijneveld
authors.forename: José Alfonso Meza
authors.initials: JA
authors.lastname: Medina
authors.forename: Amélie
authors.initials: A
authors.lastname: Liou
authors.forename: Yannick
authors.initials: Y
authors.lastname: Marie
authors.forename: Karima
authors.initials: K
authors.lastname: Mokhtari
authors.forename: Khê
authors.initials: K
authors.lastname: Hoang-Xuan
authors.forename: Marc
authors.initials: M
authors.lastname: Sanson
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Delattre
authors.forename: Ahmed
authors.initials: A
authors.lastname: Idbaih
mesh_terms: D000328:Adult; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D002888:Chromosomes, Human, Pair 19; D005091:Exons / Q000235:genetics; D005260:Female; D005910:Glioma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D012372:ROC Curve; D012189:Retrospective Studies; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D016159:Tumor Suppressor Protein p53