1. ¹Erasmus MC/Sophia Children's Hospital, Department of Pediatric Oncology/Hematology, Rotterdam, The Netherlands
2. ²Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
3. ³Department of Pediatric Oncology, Dana-Farber Cancer Institute, and Division of Hematology/Oncology, Children's Hospital, Harvard Medical School, Boston, MA, USA
4. ⁴Dutch Childhood Oncology Group (DCOG), The Hague, The Netherlands
5. ⁵Erasmus MC, Department of Clinical Genetics, Rotterdam, The Netherlands

Correspondence: Dr JPP Meijerink, Erasmus MC/Sophia Children's Hospital, Department of Pediatric Oncology/Hematology, Room: Sp 2456, Dr Molewaterplein 60, P.O. Box 2060, 3000 CB Rotterdam, The Netherlands. E-mail: j.meijerink@erasmusmc.nl

⁶These authors can be regarded as co-last authors

Received 7 July 2005; Revised 6 February 2006; Accepted 27 March 2006; Published online 4 May 2006.

Abstract

Over the last decade, genetic characterization of T-cell acute lymphoblastic leukemia (T-ALL) has led to the identification of a variety of chromosomal abnormalities. In this study, we used array-comparative genome hybridization (array-CGH) and identified a novel recurrent 9q34 amplification in 33% (12/36) of pediatric T-ALL samples, which is therefore one of the most frequent cytogenetic abnormalities observed in T-ALL thus far. The exact size of the amplified region differed among patients, but the critical region encloses 4 Mb and includes NOTCH1. The 9q34 amplification may lead to elevated expression of various genes, and MRLP41, SSNA1 and PHPT1 were found significantly expressed at higher levels. Fluorescence in situ hybridization (FISH) analysis revealed that this 9q34 amplification was in fact a 9q34 duplication on one chromosome and could be identified in 17–39 percent of leukemic cells at diagnosis. Although this leukemic subclone did not predict for poor outcome, leukemic cells carrying this duplication were still present at relapse, indicating that these cells survived chemotherapeutic treatment. Episomal NUP214-ABL1 amplification and activating mutations in NOTCH1, two other recently identified 9q34 abnormalities in T-ALL, were also detected in our patient cohort. We showed that both of these genetic abnormalities occur independently from this newly identified 9q34 duplication.