Top

Published in:

01-03-2020 | Ependymoma | Brief Communication

The TP53 p.R337H mutation is uncommon in a Brazilian cohort of pediatric patients diagnosed with ependymoma

Authors: Taciani de Almeida Magalhães, Kleiton Silva Borges, Graziella Ribeiro de Sousa, Silvia Regina Brandalise, Ana Luiza Seidinger, Carlos Alberto Scrideli, Sueli Mieko Oba-Shinjo, José Andrés Yunes, Luiz Gonzaga Tone

Published in: Neurological Sciences | Issue 3/2020

Abstract

Background

Ependymoma (EPN) is the third most common childhood cancer of the central nervous system. RELA fusion-positive EPN accounts for approximately 70% of all childhood supratentorial tumors and shows the worst prognosis among the supratentorial EPNs. TP53 mutation is infrequent in RELA fusions EPNs. In the population from the Southern region of Brazil, there is a high incidence of the germline TP53 p.R337H mutation that predisposes carriers to develop early-onset tumors. However, despite this high incidence, the frequency of this mutation among EPN patients remains to be determined. Here, we investigated the presence of the TP53 p.R337H mutation in a larger cohort of pediatric EPNs of three institutions located in the state of São Paulo, Brazil.

Methods

The TP53 p.R337H mutation was screened by conventional RT-PCR and Sanger sequencing in 49 pediatric EPNs diagnosed during the period from 1995 to 2016.

Results

We described for the first time a case of a 5-year-old girl with RELA fusion EPN with a heterozygous TP53 p.R337H mutation.

Conclusions

The present finding indicates that the TP53 p.R337H germline mutation is uncommon in patients with EPN in Brazil and screening of pediatric patients RELA fusion EPN may be informative to better understand the role of TP53 germline mutations in the development and prognosis of these tumors.

Available only for authorised users

Wu J, Armstrong TS, Gilbert MR (2016) Biology and management of ependymomas. Neuro Oncol 18:902–913. https://doi.org/10.1093/neuonc/now016CrossRefPubMedPubMedCentral

Pajtler KW, Witt H, Sill M et al (2015) Molecular classification of ependymal tumors across all CNS compartments, histopathological grades, and age groups. Cancer Cell 27:728–743. https://doi.org/10.1016/j.ccell.2015.04.002CrossRefPubMedPubMedCentral

Parker M, Mohankumar KM, Punchihewa C et al (2014) C11orf95–RELA fusions drive oncogenic NF-κB signalling in ependymoma. Nature 506:451–455. https://doi.org/10.1038/nature13109CrossRefPubMedPubMedCentral

Witt H, Gramatzki D, Hentschel B et al (2018) DNA methylation-based classification of ependymomas in adulthood: implications for diagnosis and treatment. Neuro Oncol 20:1616–1624. https://doi.org/10.1093/neuonc/noy118CrossRefPubMedPubMedCentral

Fink K, Rushing E, Schold SC, Nisen P (1996) Infrequency of p53 gene mutations in ependymomas. J Neurooncol 27:111–115. https://doi.org/10.1007/BF00177473CrossRefPubMed

Nozaki M, Tada M, Matsumoto R et al (1998) Rare occurrence of inactivating p53 gene mutations in primary non-astrocytic tumors of the central nervous system: reappraisal by yeast functional assay. Acta Neuropathol 95:291–296. https://doi.org/10.1007/s004010050800CrossRefPubMed

Tzaridis T, Milde T, Pajtler KW, et al Low-dose actinomycin-D treatment re-establishes the tumour-suppressive function of P53 in RELA-positive ependymoma. 7:

McBride KA, Ballinger ML, Killick E et al (2014) Li-Fraumeni syndrome: cancer risk assessment and clinical management. Nat Rev Clin Oncol 11:260–271. https://doi.org/10.1038/nrclinonc.2014.41CrossRefPubMed

Ferrarini A, Auteri-Kaczmarek A, Pica A et al (2011) Early occurrence of lung adenocarcinoma and breast cancer after radiotherapy of a chest wall sarcoma in a patient with a de novo germline mutation in TP53. Fam Cancer 10:187–192. https://doi.org/10.1007/s10689-010-9415-9CrossRefPubMed

10.

Henry E, Villalobos V, Million L et al (2012) Chest wall leiomyosarcoma after breast-conservative therapy for early-stage breast cancer in a young woman with Li-Fraumeni syndrome. J Natl Compr Cancer Netw 10:939–942. https://doi.org/10.6004/jnccn.2012.0097CrossRef

11.

Heymann S, Delaloge S, Rahal A et al (2010) Radio-induced malignancies after breast cancer postoperative radiotherapy in patients with Li-Fraumeni syndrome. Radiat Oncol 5:104. https://doi.org/10.1186/1748-717X-5-104CrossRefPubMedPubMedCentral

12.

Limacher J-M, Frebourg T, Natarajan-Ame S, Bergerat J-P (2001) Two metachronous tumors in the radiotherapy fields of a patient with Li-Fraumeni syndrome. Int J Cancer 96:238–242. https://doi.org/10.1002/ijc.1021CrossRefPubMed

13.

Salmon A, Amikam D, Sodha N et al (2007) Rapid development of post-radiotherapy sarcoma and breast cancer in a patient with a novel germline ‘De-Novo’ TP53 mutation. Clin Oncol 19:490–493. https://doi.org/10.1016/j.clon.2007.05.001CrossRef

14.

Custódio G, Parise GA, Kiesel Filho N et al (2013) Impact of neonatal screening and surveillance for the TP53 R337H mutation on early detection of childhood adrenocortical tumors. J Clin Oncol 31:2619–2626. https://doi.org/10.1200/JCO.2012.46.3711CrossRefPubMedPubMedCentral

15.

Achatz MIW, Olivier M, Le Calvez F et al (2007) The TP53 mutation, R337H, is associated with Li-Fraumeni and Li-Fraumeni-like syndromes in Brazilian families. Cancer Lett 245:96–102. https://doi.org/10.1016/j.canlet.2005.12.039CrossRefPubMed

16.

Giacomazzi J, Graudenz MS, Osorio CABT et al (2014) Prevalence of the TP53 p.R337H mutation in breast cancer patients in Brazil. PLoS One 9:e99893. https://doi.org/10.1371/journal.pone.0099893CrossRefPubMedPubMedCentral

17.

Seidinger AL, Mastellaro MJ, Paschoal Fortes F et al (2011) Association of the highly prevalent TP53 R337H mutation with pediatric choroid plexus carcinoma and osteosarcoma in Southeast Brazil. Cancer 117:2228–2235. https://doi.org/10.1002/cncr.25826CrossRefPubMed

18.

Formiga MN d C, de Andrade KC, Kowalski LP, Achatz MI (2017) Frequency of thyroid carcinoma in Brazilian TP53 p.R337H carriers with Li Fraumeni syndrome. JAMA Oncol 3:1400. https://doi.org/10.1001/jamaoncol.2016.6389CrossRefPubMedPubMedCentral

19.

Seidinger AL, Fortes FP, Mastellaro MJ et al (2015) Occurrence of neuroblastoma among TP53 p.R337H carriers. PLoS One 10:e0140356. https://doi.org/10.1371/journal.pone.0140356CrossRefPubMedPubMedCentral

20.

Zhukova N, Ramaswamy V, Remke M et al (2013) Subgroup-specific prognostic implications of TP53 mutation in medulloblastoma. J Clin Oncol 31:2927–2935. https://doi.org/10.1200/JCO.2012.48.5052CrossRefPubMedPubMedCentral

21.

Hosoya T, Kambe A, Nishimura Y et al (2018) Pediatric case of Li-Fraumeni syndrome complicated with supratentorial anaplastic ependymoma. World Neurosurg 120:125–128. https://doi.org/10.1016/j.wneu.2018.08.203CrossRefPubMed

22.

Metzger AK, Sheffield VC, Duyk G et al (1991) Identification of a germ-line mutation in the p53 gene in a patient with an intracranial ependymoma. Proc Natl Acad Sci 88:7825–7829. https://doi.org/10.1073/pnas.88.17.7825CrossRefPubMed

23.

Assumpção JG, Seidinger AL, Mastellaro MJ et al (2008) Association of the germline TP53 R337H mutation with breast cancer in southern Brazil. BMC Cancer 8:1–6. https://doi.org/10.1186/1471-2407-8-357CrossRef

24.

Imamura J, Nakamura H, Koeffler HP et al (1993) Mutation of the p53 gene in neuroblastoma and its relationship with N-myc amplification. Cancer Res 53:4053–4058PubMed

25.

Evans DGR (2005) Malignant transformation and new primary tumours after therapeutic radiation for benign disease: substantial risks in certain tumour prone syndromes. J Med Genet 43:289–294. https://doi.org/10.1136/jmg.2005.03631CrossRefPubMedPubMedCentral

Title: The TP53 p.R337H mutation is uncommon in a Brazilian cohort of pediatric patients diagnosed with ependymoma
Authors: Taciani de Almeida Magalhães
Kleiton Silva Borges
Graziella Ribeiro de Sousa
Silvia Regina Brandalise
Ana Luiza Seidinger
Carlos Alberto Scrideli
Sueli Mieko Oba-Shinjo
José Andrés Yunes
Luiz Gonzaga Tone
Publication date: 01-03-2020
Publisher: Springer International Publishing
Keywords: Ependymoma
Ependymoma
Ependymoma
Published in: Neurological Sciences / Issue 3/2020
Print ISSN: 1590-1874
Electronic ISSN: 1590-3478
DOI: https://doi.org/10.1007/s10072-019-04112-x

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

The TP53 p.R337H mutation is uncommon in a Brazilian cohort of pediatric patients diagnosed with ependymoma

Abstract

Background

Methods

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 3/2020

SPG8 mutations in Italian families: clinical data and literature review

Prognostic role of Mini-Mental State Pediatric Examination (MMSPE) on neuropsychological functioning

Differential expression of STAT3 gene and its regulatory long non-coding RNAs, namely lnc-DC and THRIL, in two eastern Iranian ethnicities with multiple sclerosis

Anti-GAD epileptic encephalopathy in a toddler with Parry-Romberg syndrome

Highlights of the issue 3, 2020

The role of virtual reality on outcomes in rehabilitation of Parkinson’s disease: meta-analysis and systematic review in 1031 participants