Delineation of a 1Mb breakpoint region at 1p13 in Wilms tumors by fine-tiling oligonucleotide array CGH.
Wilms tumor karyotypes frequently exhibit recurrent, large-scale chromosomal imbalances, among the most common of which are concurrent loss of 1p and gain of 1q. We have previously identified a novel breakpoint at 1p13 by 1 Mb-spaced array CGH, and have now undertaken a fine-tiling oligonucleotide array approach to map the region accurately in four tumors exhibiting rearrangements at this locus. The use of a 10 bp-spaced platform revealed that all four tumors in fact harbored different breakpoints, which targeted intragenic sequences in PHTF1, DCLRE1B, and NRAS, and an intergenic region immediately downstream of TRIM33. All four genes and breakpoints were within the 1.78 Mb intervals identified by the genome-wide BAC arrays. The precise breakpoint interval was in each case mapped to a 200-1,200 bp region and was confirmed for one case to lie within intron 3 of DCLRE1B by quantitative PCR. Analysis of local genome architecture revealed no convincing conservation of repetitive sequences or specific translocation/recombination-associated elements within the breakpoint regions. This study highlights the power of fine-tiling oligonucleotide arrays to delineate breakpoint regions identified by genome-wide screens.
Natrajan
Rachael
R
Paediatric Oncology, Institute of Cancer Research/Royal Marsden NHS Trust, Sutton, UK.
Williams
Richard D
RD
Grigoriadis
Anita
A
Mackay
Alan
A
Fenwick
Kerry
K
Ashworth
Alan
A
Dome
Jeffrey S
JS
Grundy
Paul E
PE
Pritchard-Jones
Kathy
K
Jones
Chris
C
D019457:Chromosome Breakage; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D018628:Gene Dosage; D006801:Humans; D009693:Nucleic Acid Hybridization / Q000379:methods; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods* / Q000592:standards; D011995:Recombination, Genetic; D012091:Repetitive Sequences, Nucleic Acid; D014178:Translocation, Genetic; D009396:Wilms Tumor / Q000235:genetics*