By sequencing the genome of a mouse with cancer, a team of researchers that includes Elaine Mardis and Richard Wilson has also uncovered mutations that affect human cancers, press release from Washington University in St. Louis says. The study, which appears in the Journal of Clinical Investigation, looked at a mouse model of acute promyelocytic leukemia. The researchers inserted a mutated human gene called PML-RARA, known to initiate APL in humans, into mice and waited for leukemia to develop, the release says. As they waited, the researchers tried to find cooperating mutations in the mouse bone marrow cells to determine if they also occur in humans. "When co-authors Richard Wilson and Elaine Mardis … and their colleagues sequenced the genome of the mouse tumor cells, they found genetic mutations in three genes, each of which alter a single letter in the DNA sequence and disrupt the instructions for making proteins," the university says. "One of these mutations, in the Jak1 gene, also occurred in six of 89 other APL mouse tumors they studied. Moreover, the mutation was identical to one that other research teams recently identified in one patient with APL and in other patients with acute lymphoblastic leukemia." The researchers suggest that since the mutation has been shown to occur in other mouse tumor samples and in patients with leukemia, this mutation in a driver of the disease. The team also found a deletion in the Kdm6a gene in the mouse tumor genome — deletions in the same gene have also been associated with human cancer, the press release adds. In the future, the researchers say, they will continue to use mouse models in conjunction with sequencing human cancer genomes in order to help them determine which mutations are important for disease progression. "If we find the same mutations in human cancers and in a mouse model of the disease, then we know they are likely to be relevant, even if we've only seen the mutations in a small fraction of patients," Wilson says.
'Of Mice and Men'
Mar 29, 2011