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Delineation of a 1Mb breakpoint region at 1p13 in Wilms tumors by fine‐tiling oligonucleotide array CGH
Author(s) -
Natrajan Rachael,
Williams Richard D.,
Grigoriadis Anita,
Mackay Alan,
Fenwick Kerry,
Ashworth Alan,
Dome Jeffrey S.,
Grundy Paul E.,
PritchardJones Kathy,
Jones Chris
Publication year - 2007
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.20446
Subject(s) - breakpoint , biology , genetics , tiling array , genome , copy number variation , interspersed repeat , chromosomal translocation , gene , computational biology , dna microarray , human genome , gene expression
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. © 2007 Wiley‐Liss, Inc.