DSCC1_Tumour_sequencing-sc-2013-03-07T15:52:42Z-2560
DSCC1_Tumour_sequencing
We have shown that Dscc1 knockout mice have a 5-fold increase in micronucleated red blood cells, which is a good indicator of genomic instability and therefore cancer predisposition. DSCC1 mutations have been identified in a variety of human malignancies so we aged a cohort of these mice to test whether they were tumour prone. The mutants showed reduced survival compared to wildtype mice and the large majority (98%) developed sarcomas and/or lymphomas. Dscc1 (defective in sister chromatid cohesion 1) has been shown to load PCNA onto primed templates and thus regulates the velocity, spacing and restart activity of replication forks. In addition, Dscc1 may couple DNA replication to sister chromatid cohesion through regulation of the acetylation of the cohesin subunit SMC3. Knockout of the yeast homolog, DCC1, results in tetraploidy. We have extracted DNA from a subset of Dscc1 mutant mouse tumours with a high tumour:stromal cell ratio and wish to sequence these, together with matched normal DNA, in order to understand how Dscc1-deficiency contributes to the process of tumourigenesis. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/
We have shown that Dscc1 knockout mice have a 5-fold increase in micronucleated red blood cells, which is a good indicator of genomic instability and therefore cancer predisposition. DSCC1 mutations have been identified in a variety of human malignancies so we aged a cohort of these mice to test whether they were tumour prone. The mutants showed reduced survival compared to wildtype mice and the large majority (98%) developed sarcomas and/or lymphomas. Dscc1 (defective in sister chromatid cohesion 1) has been shown to load PCNA onto primed templates and thus regulates the velocity, spacing and restart activity of replication forks. In addition, Dscc1 may couple DNA replication to sister chromatid cohesion through regulation of the acetylation of the cohesin subunit SMC3. Knockout of the yeast homolog, DCC1, results in tetraploidy. We have extracted DNA from a subset of Dscc1 mutant mouse tumours with a high tumour:stromal cell ratio and wish to sequence these, together with matched normal DNA, in order to understand how Dscc1-deficiency contributes to the process of tumourigenesis.