Array CGH profiling of favourable histology Wilms tumours reveals novel gains and losses associated with relapse.
Despite the excellent survival of Wilms tumour patients treated with multimodality therapy, approximately 15% will suffer from tumour relapse, where response rates are markedly reduced. We have carried out microarray-based comparative genomic hybridisation on a series of 76 Wilms tumour samples, enriched for cases which recurred, to identify changes in DNA copy number associated with clinical outcome. Using 1Mb-spaced genome-wide BAC arrays, the most significantly different genomic changes between favourable histology tumours that did (n = 37), and did not (n = 39), subsequently relapse were gains on 1q, and novel deletions at 12q24 and 18q21. Further relapse-associated loci included losses at 1q32.1, 2q36.3-2q37.1, and gain at 13q31. 1q gains correlated strongly with loss of 1p and/or 16q. In 3 of 11 cases with concurrent 1p(-)/1q(+), a breakpoint was identified at 1p13. Multiple low-level sub-megabase gains along the length of 1q were identified using chromosome 1 tiling-path arrays. One such recurrent region at 1q22-q23.1 included candidate genes RAB25, NES, CRABP2, HDGF and NTRK1, which were screened for mRNA expression using quantitative RT-PCR. These data provide a high-resolution catalogue of genomic copy number changes in relapsing favourable histology Wilms tumours.
Natrajan
R
R
Paediatric Oncology, Institute of Cancer Research/Royal Marsden NHS Trust, Sutton, Surrey SM2 5NG, UK.
Williams
R D
RD
Hing
S N
SN
Mackay
A
A
Reis-Filho
J S
JS
Fenwick
K
K
Iravani
M
M
Valgeirsson
H
H
Grigoriadis
A
A
Langford
C F
CF
Dovey
O
O
Gregory
S G
SG
Weber
B L
BL
Ashworth
A
A
Grundy
P E
PE
Pritchard-Jones
K
K
Jones
C
C
D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D016162:Genes, Wilms Tumor / Q000502:physiology; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology; D009364:Neoplasm Recurrence, Local / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis; D016896:Treatment Outcome; D009396:Wilms Tumor / Q000235:genetics* / Q000473:pathology
D004273:DNA, Neoplasm; D012333:RNA, Messenger; D012334:RNA, Neoplasm