Submitted February 28, 2007
Accepted August 24, 2007
NOTCH1 mutation can be an early, pre-natal genetic event in T-ALL
Minenori Eguchi-Ishimae, Mariko Eguchi, Helena Kempski, and Mel Greaves*
Section of Haemato-Oncology, The Institute of Cancer Research, London, United Kingdom
Molecular Haematology and Cancer Biology Unit, Institute of Child Health, London, United Kingdom
* Corresponding author; email: mel.greaves{at}icr.ac.uk.
NOTCH1 mutations are common in T-ALL. Twin studies and retrospective screening of neonatal blood spots provide evidence that fusion genes and other chromosomal abnormalities associated with pediatric leukemias can originate prenatally. Whether this is also the case for NOTCH1 mutations is unknown. Eleven cases of T-ALL were screened for NOTCH1 mutations and four (36%) had mutations in either the HD or PEST domains. Of these four, three could be amplified by mutation-specific PCR primers. In one of these three, with the highest sensitivity, NOTCH1 mutation was detected in neonatal blood spots. In this patient, the blood spot was negative for SIL-TAL1 fusion, present concomitant with NOTCH1 mutation, in the diagnostic sample. We conclude that NOTCH1 can be an early or initiating event in T-ALL arising prenatally, to be complemented by a postnatal SIL-TAL1 fusion.
