[PDF][PDF] Trp53R172H and KrasG12D cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in mice

SR Hingorani, L Wang, AS Multani, C Combs… - Cancer cell, 2005 - cell.com
SR Hingorani, L Wang, AS Multani, C Combs, TB Deramaudt, RH Hruban, AK Rustgi…
Cancer cell, 2005cell.com
To define the genetic requirements for pancreatic ductal adenocarcinoma (PDA), we have
targeted concomitant endogenous expression of Trp53 R172H and Kras G12D to the mouse
pancreas, revealing the cooperative development of invasive and widely metastatic
carcinoma that recapitulates the human disease. The primary carcinomas and metastases
demonstrate a high degree of genomic instability manifested by nonreciprocal translocations
without obvious telomere erosion—hallmarks of human carcinomas not typically observed in …
Summary
To define the genetic requirements for pancreatic ductal adenocarcinoma (PDA), we have targeted concomitant endogenous expression of Trp53R172H and KrasG12D to the mouse pancreas, revealing the cooperative development of invasive and widely metastatic carcinoma that recapitulates the human disease. The primary carcinomas and metastases demonstrate a high degree of genomic instability manifested by nonreciprocal translocations without obvious telomere erosion—hallmarks of human carcinomas not typically observed in mice. No mutations were discovered in other cardinal tumor suppressor gene pathways, which, together with previous results, suggests that there are distinct genetic pathways to PDA with different biological behaviors. These findings have clear implications for understanding mechanisms of disease pathogenesis, and for the development of detection and targeted treatment strategies.
cell.com