Previous Work
Previous work on Wilms tumour genomics and preclinical models
Former research in the lab included a programme specifically aimed at understanding the genomics of the childhood renal cancer Wilms tumour, and translating this knowledge into clinical benefit through novel models systems and drug development.
We published the first, and largest, genome-wide copy number profiling studies on Wilms tumours and their precursor lesions, nephrogenic rests, identifying numerous candidate genetic alterations which may used in the diagnostic, prognostic/predictive and therapeutic settings.
In particular, we have demonstrated the critical dependence of Wilms tumour cells on signalling through the IGF1-receptor, and have developed the first orthotopic models of the disease for preclinical evaluation of small molecule inhibitors of this pathway.
Selected publications
1. Bielen A, Box G, Perryman L, Popov S, Jamin Y, Jury SA, Valenti M, de Haven Brandon A, Martins V, Jeay S, Raynaud F, Hofmann F, Robinson S, Eccles SA and Jones C (submitted) “Dependence of Wilms tumour cells on signalling through IGF1R in an orthotopic xenograft model targetable by specific receptor inhibition”
2. Vuononvirta R, Sebire NJ, Messahel B, Perusinghe N, Reis-Filho JS, Pritchard-Jones K, Vujanic GM and Jones C (2009) “Expression of HGF and its receptor MET in Wilms tumours and nephrogenic rests reflects their roles in kidney development” Clin Cancer Res 15:2723-2730
3. Vuononvirta R, Sebire NJ, Dallosso AR, Reis-Filho JS, Williams RD, Mackay A, Fenwick K, Grigoriadis A, Ashworth A, Pritchard-Jones K, Brown KM, Vujanic GM and Jones C (2008) “Perilobar nephrogenic rests are non-obligate molecular genetic precursor lesions of IGF2-associated Wilms tumours” Clin Cancer Res 14:7635-7644
4. Natrajan R*, Williams RD*, Grigoriadis A, Mackay A, Fenwick K, Ashworth A, Dome JS, Grundy PE, Pritchard-Jones K and Jones C (2007) “Delineation of a 1Mb breakpoint region at 1p13 in Wilms tumours by fine-tiling oligonucleotide array CGH” Genes Chrom Cancer 46:607-615
5. Natrajan R, Little SE, Sodha N, Reis-Filho JS, Mackay A, Fenwick K, Ashworth A, Perlman EJ, Dome JS, Grundy PE, Pritchard-Jones K, and Jones C (2007) “Genomic changes as assessed by array CGH associated with the progression or relapse of Wilms tumour” J Pathol 211:52-59
6. Natrajan R, Reis-Filho JS, Little SE, Messahel B, Brundler M-A, Dome JS, Grundy PE, Vujanic GM, Pritchard-Jones K, and Jones C (2006) “Blastemal expression of type I insulin-like growth factor receptor in Wilms tumours is driven by increased copy number and correlates with relapse” Cancer Res 66:11148-11155
7. Natrajan R, Williams RD, Hing SN, Mackay A, Reis-Filho JS, Fenwick K, Iravani M, Valgeirsson H, Grigoriadis A, Langford CF, Dovey O, Gregory SG, Weber BL, Ashworth A, Grundy PE, Pritchard-Jones K, and Jones C (2006) “Array CGH profiling of favourable histology Wilms tumours reveals novel gains and losses associated with relapse” J Pathol 210:49-58
Genomic profiling of paediatric high grade glioma
To make the greatest progress in these rare tumours, it would be beneficial to pool as much data as possible, in order to better define the molecular alterations driving this disease.
