Open Access Open Badges Research article

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

Marcela Braga Mansur1, Rocio Hassan2, Thayana C Barbosa1, Alessandra Splendore3, Patricia Y Jotta4, José Andrés Yunes4, Joseph L Wiemels5 and Maria S Pombo-de-Oliveira16*

Author Affiliations

1 Paediatric Haematology-Oncology Program, Research Centre, Instituto Nacional de Câncer, Rio de Janeiro, RJ, Brazil

2 Bone Marrow Transplantation Centre (CEMO), Instituto Nacional de Câncer, Rio de Janeiro, RJ, Brazil

3 Human Genome Studies Center, Instituto de Biociências, Universidade de São Paulo, São Paulo, SP, Brazil

4 Molecular Biology Laboratory, Centro Infantil Boldrini, Campinas, SP, Brazil

5 Laboratory for Molecular Epidemiology, Department of Epidemiology & Biostatistics, University of California, San Francisco, CA, USA

6 Paediatric Haematology-Oncology Program, 6th floor, Research, Center, Instituto Nacional de Câncer-MS, Rua André Cavalcanti, 37, 20231-050 Rio de Janeiro, RJ, Brazil

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BMC Cancer 2012, 12:9  doi:10.1186/1471-2407-12-9

Published: 6 January 2012



Molecular 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.


T-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.


The 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.


NOTCH1 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.