The correlation pattern of acquired copy number changes in 164 ETV6/RUNX1-positive childhood acute lymphoblastic leukemias.
The ETV6/RUNX1 fusion gene, present in 25% of B-lineage childhood acute lymphoblastic leukemia (ALL), is thought to represent an initiating event, which requires additional genetic changes for leukemia development. To identify additional genetic alterations, 24 ETV6/RUNX1-positive ALLs were analyzed using 500K single nucleotide polymorphism arrays. The results were combined with previously published data sets, allowing us to ascertain genomic copy number aberrations (CNAs) in 164 cases. In total, 45 recurrent CNAs were identified with an average number of 3.5 recurrent changes per case (range 0-13). Twenty-six percent of cases displayed a set of recurrent CNAs identical to that of other cases in the data set. The majority (74%), however, displayed a unique pattern of recurrent CNAs, indicating a large heterogeneity within this ALL subtype. As previously demonstrated, alterations targeting genes involved in B-cell development were common (present in 28% of cases). However, the combined analysis also identified alterations affecting nuclear hormone response (24%) to be a characteristic feature of ETV6/RUNX1-positive ALL. Studying the correlation pattern of the CNAs allowed us to highlight significant positive and negative correlations between specific aberrations. Furthermore, oncogenetic tree models identified ETV6, CDKN2A/B, PAX5, del(6q) and +16 as possible early events in the leukemogenic process.
Department of Clinical Genetics, University and Regional Laboratories, Skåne University Hospital, Lund University, Lund, Sweden. henrik.lilljebjorn@med.lu.se
Henrik
H
Lilljebjörn
Charlotte
C
Soneson
Anna
A
Andersson
Jesper
J
Heldrup
Mikael
M
Behrendtz
Norihiko
N
Kawamata
Seishi
S
Ogawa
H Phillip
HP
Koeffler
Felix
F
Mitelman
Bertil
B
Johansson
Magnus
M
Fontes
Thoas
T
Fioretos
D000293:Adolescent; D045744:Cell Line, Tumor; D002648:Child; D002675:Child, Preschool; D016000:Cluster Analysis; D050676:Core Binding Factor Alpha 2 Subunit; D005260:Female; D018628:Gene Dosage; D018740:Genetic Heterogeneity; D023281:Genomics; D006801:Humans; D008297:Male; D015514:Oncogene Proteins, Fusion / Q000145:classification / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000473:pathology; D012008:Recurrence; D015398:Signal Transduction / Q000235:genetics; D000097764:ETS Translocation Variant 6 Protein
D050676:Core Binding Factor Alpha 2 Subunit; D015514:Oncogene Proteins, Fusion; C102421:TEL-AML1 fusion protein; D000097764:ETS Translocation Variant 6 Protein