Scientists has developed a more human-like mouse model of cancer they say will aid the search for cancer-causing genes and improve the predictive value of laboratory drug testing.
The study was conducted by a team of researchers including Richard Maser, Ronald A. DePinho, Lynda Chin at the Dana-Farber Cancer Institute.
Conventional mouse models are developed by transferring a cancer-causing oncogene into a mouse embryo.
"You plug it into the mouse, and lo and behold, it gets cancer. But that's rigging the game -- it's not identical to the process by which tumors normally arise," Maser said.
These tumors don’t have some important characteristics of human tumors, such as genomic instability, pieces of chromosomes breaking apart and reattaching, which lead to defects like missing genes or extra copies of genes some of which are key to the tumors’ formation.
As part of the study, researchers used gene knockouts to develop mice whose cells don’t have molecules which guard the genome from instability in the DNA.
Researchers created mice which formed T-cell acute lymphoblastic leukemia/lymphoma, or T-ALL, and the cancer cells showed ‘rampant genome instability’ resulting in intricate pattern of mutations, chromosomal rearrangements, gene amplifications and gene deletions similar to those in human solid tumors.
Researchers characterized these mouse tumors by performing high-resolution array-CGH profiling, a genome-scanning technology that can define regions of DNA abnormalities.
Researchers then compared the patterns of chromosomal changes in the mice with patterns observed in more than 400 human tumor specimens, including melanoma, lung, colon, and pancreatic cancers, and multiple myeloma.
