Impact of complex NOTCH1 mutations on survival in paediatric T-cell leukaemia

BMC Cancer

Research Article

Rocio Hassan¹  Alessandra Splendore²  Joseph L Wiemels³  José Andrés Yunes⁴  Patricia Y Jotta⁴  Marcela Braga Mansur⁵  Thayana C Barbosa⁵  Maria S Pombo-de-Oliveira⁶ 

[1] Bone Marrow Transplantation Centre (CEMO), Instituto Nacional de Câncer, Rio de Janeiro, RJ, Brazil;Human Genome Studies Center, Instituto de Biociências, Universidade de São Paulo, São Paulo, SP, Brazil;Laboratory for Molecular Epidemiology, Department of Epidemiology & Biostatistics, University of California, San Francisco, CA, USA;Molecular Biology Laboratory, Centro Infantil Boldrini, Campinas, SP, Brazil;Paediatric Haematology-Oncology Program, Research Centre, Instituto Nacional de Câncer, Rio de Janeiro, RJ, Brazil;Paediatric Haematology-Oncology Program, Research Centre, Instituto Nacional de Câncer, Rio de Janeiro, RJ, Brazil;Paediatric Haematology-Oncology Program, Instituto Nacional de Câncer-MS, 6th floor, Research, Center, Rua André Cavalcanti, 37, 20231-050, Rio de Janeiro, RJ, Brazil;

关键词: Overall Survival;    KRAS Mutation;    Molecular Alteration;    PTEN Mutation;    Complex Mutation;   

DOI  :  10.1186/1471-2407-12-9

 received in 2011-06-02, accepted in 2012-01-06,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundMolecular alterations occur frequently in T-ALL and the potential impact of those abnormalities on outcome is still controversial. The current study aimed to test whether NOTCH1 mutations and additional molecular abnormalities would impact T-ALL outcome in a series of 138 T-ALL paediatric cases.MethodsT-ALL subtypes, status of SIL-TAL1 fusion, ectopic expression of TLX3, and mutations in FBXW7, KRAS, PTEN and NOTCH1 were assessed as overall survival (OS) and event-free survival (EFS) prognostic factors. OS and EFS were determined using the Kaplan-Meier method and compared using the log-rank test.ResultsThe frequencies of mutations were 43.5% for NOTCH1, while FBXW7, KRAS and PTEN exhibited frequencies of 19.1%, 9.5% and 9.4%, respectively. In 78.3% of cases, the coexistence of NOTCH1 mutations and other molecular alterations was observed. In multivariate analysis no statistical association was revealed between NOTCH1 mutations and any other variable analyzed. The mean length of the follow-up was 68.4 months and the OS was 50.7%. SIL-TAL1 was identified as an adverse prognostic factor. NOTCH1 mutation status was not associated with outcome, while the presence of NOTCH1 complex mutations (indels) were associated with a longer overall survival (p = 0.031) than point mutations.ConclusionNOTCH1 mutations alone or in combination with FBXW7 did not impact T-ALL prognosis. Nevertheless, complex NOTCH1 mutations appear to have a positive impact on OS and the SIL-TAL1 fusion was validated as a negative prognostic marker in our series of T-ALL.

【 授权许可】

Unknown   
© Mansur et al; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.