{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T15:31:38Z","timestamp":1764603098555},"reference-count":37,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2012,1,6]],"date-time":"2012-01-06T00:00:00Z","timestamp":1325808000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Cancer"],"published-print":{"date-parts":[[2012,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>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 <jats:italic>NOTCH1<\/jats:italic> mutations and additional molecular abnormalities would impact T-ALL outcome in a series of 138 T-ALL paediatric cases.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>T-ALL subtypes, status of <jats:italic>SIL-TAL1<\/jats:italic> fusion, ectopic expression of <jats:italic>TLX3<\/jats:italic>, and mutations in <jats:italic>FBXW7<\/jats:italic>, <jats:italic>KRAS<\/jats:italic>, <jats:italic>PTEN<\/jats:italic> and <jats:italic>NOTCH1<\/jats:italic> 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.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>The frequencies of mutations were 43.5% for <jats:italic>NOTCH1<\/jats:italic>, while <jats:italic>FBXW7<\/jats:italic>, <jats:italic>KRAS<\/jats:italic> and <jats:italic>PTEN<\/jats:italic> exhibited frequencies of 19.1%, 9.5% and 9.4%, respectively. In 78.3% of cases, the coexistence of <jats:italic>NOTCH1<\/jats:italic> mutations and other molecular alterations was observed. In multivariate analysis no statistical association was revealed between <jats:italic>NOTCH1<\/jats:italic> mutations and any other variable analyzed. The mean length of the follow-up was 68.4 months and the OS was 50.7%. <jats:italic>SIL-TAL1<\/jats:italic> was identified as an adverse prognostic factor. <jats:italic>NOTCH1<\/jats:italic> mutation status was not associated with outcome, while the presence of <jats:italic>NOTCH1<\/jats:italic> complex mutations (indels) were associated with a longer overall survival (<jats:italic>p<\/jats:italic> = 0.031) than point mutations.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>\n              <jats:italic>NOTCH1<\/jats:italic> mutations alone or in combination with <jats:italic>FBXW7<\/jats:italic> did not impact T-ALL prognosis. Nevertheless, complex <jats:italic>NOTCH1<\/jats:italic> mutations appear to have a positive impact on OS and the <jats:italic>SIL-TAL1<\/jats:italic> fusion was validated as a negative prognostic marker in our series of T-ALL.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1471-2407-12-9","type":"journal-article","created":{"date-parts":[[2012,1,6]],"date-time":"2012-01-06T19:18:28Z","timestamp":1325877508000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Impact of complex NOTCH1 mutations on survival in paediatric T-cell leukaemia"],"prefix":"10.1186","volume":"12","author":[{"given":"Marcela Braga","family":"Mansur","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rocio","family":"Hassan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thayana C","family":"Barbosa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra","family":"Splendore","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patricia Y","family":"Jotta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 Andr\u00e9s","family":"Yunes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph L","family":"Wiemels","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria S","family":"Pombo-de-Oliveira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2012,1,6]]},"reference":[{"issue":"5","key":"3067_CR1","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1038\/nri2304","volume":"8","author":"I Aifantis","year":"2008","unstructured":"Aifantis I, Raetz E, Buonamici S: Molecular pathogenesis of T-cell leukaemia and lymphoma. 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