Tiling resolution array comparative genomic hybridization, expression and methylation analyses of dup(1q) in Burkitt lymphomas and pediatric high hyperdiploid acute lymphoblastic leukemias reveal clustered near-centromeric breakpoints and overexpression of genes in 1q22-32.3.
Although gain of 1q occurs in 25% of Burkitt lymphomas (BLs) and 10% of pediatric high hyperdiploid acute lymphoblastic leukemias (ALLs), little is known about the origin, molecular genetic characteristics and functional outcome of dup(1q) in these disorders. Ten dup(1q)-positive BLs/ALLs were investigated by tiling resolution (32k) array CGH analysis, which revealed that the proximal breakpoints in all cases were near-centromeric, in eight of them clustering within a 1.4 Mb segment in 1q12-21.1. The 1q distal breakpoints were heterogeneous, being more distal in the ALLs than in the BLs. The minimally gained segments in the ALLs and BLs were 57.4 Mb [dup(1)(q22q32.3)] and 35 Mb [dup(1)(q12q25.2)], respectively. Satellite II DNA on 1q was not hypomethylated, as ascertained by Southern blot analyses of 15 BLs/ALLs with and without gain of 1q, indicating that aberrant methylation was not involved in the origin of dup(1q), as previously suggested for other neoplasms with 1q rearrangements. Global gene expression analyses revealed that five genes in the minimally 57.4 Mb gained region--B4GALT3, DAP3, RGS16, TMEM183A and UCK2--were significantly overexpressed in dup(1q)-positive ALLs compared with high hyperdiploid ALLs without dup(1q). The DAP3 and UCK2 genes were among the most overexpressed genes in the BL case with gain of 1q investigated. The DAP3 protein has been reported to be highly expressed in invasive glioblastoma multiforme cells, whereas expression of the UCK2 protein has been correlated with sensitivity to anticancer drugs. However, involvement of these genes in dup(1q)-positive ALLs and BLs has previously not been reported.
Davidsson
Josef
J
Department of Clinical Genetics, Lund University Hospital, Sweden. josef.davidsson@med.lu.se
Andersson
Anna
A
Paulsson
Kajsa
K
Heidenblad
Markus
M
Isaksson
Margareth
M
Borg
Ake
A
Heldrup
Jesper
J
Behrendtz
Mikael
M
Panagopoulos
Ioannis
I
Fioretos
Thoas
T
Johansson
Bertil
B
D000293:Adolescent; D000328:Adult; D002051:Burkitt Lymphoma / Q000235:genetics* / Q000378:metabolism; D002503:Centromere / Q000235:genetics* / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation; D004171:Diploidy; D005260:Female; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000378:metabolism
D009363:Neoplasm Proteins