Molecular Genetics of Germ Cell Tumours and Cell Cycle Regulation
My laboratory is focusing on two areas of investigation: a cell cycle regulated kinase, designated TTK; and the study of inherited cancer, particularly germ cell cancer of the testis. TTK is a ubiquitously expressed kinase that is regulated in the cell cycle, with maximum activity in G2/M. It is most highly related to the yeast kinase RPK1, which appears to play a role in S. cerevisiae cell cycle control. We are now attempting to prove that TTK plays a role in the mammalian cell cycle. In addition, in collaboration with Robert Martin (Strasbourg, France), we are determining whether TTK can rescue RPK1-deficient yeast strains.
Germ cell tumors (GCT) of the testis are inherited in some cases. The transmission pattern may be autosomal dominant or recessive. We are part of an international group (UK, Canada, Norway and Australia) that is attempting to map the location(s) of the putative susceptibility genes by linkage analysis. My laboratory is also examining the molecular changes found in sporadic GCT.
In a related project, we have examined a family with inherited melanoma in collaboration with Norman Lassam. We have found a novel mutation in the p16INK4 gene that segregates with melanoma in this family. We have also demonstrated that the protein encoded by the mutant gene is dysfunctional. Our laboratories are continuing to collaborate on this and other familial malignancies.
Graduate Students:
- Ronald Agetap
- Isabel Lokody
Selected References:
Link to Pubmed PublicationsHogg, D., Guidos, C., Bailey, D., Amendola, A., Groves, T., Davidson, J., Scmandt, R., and Mills, G.B. 1994. Cell Cycle Dependent Regulation of the Protein Kinase ITK. Oncogene, 9:89-96.
Liu, L., Lassam, N., Slingerland, J., Bailey, D., Cole, D., Jenkins, R., and Hogg, D. 1995. Germline p16INK4A mutation and protein dysfunction in a family with inherited melanoma. Oncogene, 11:405-412.
Peng, H.-Q., Bailey, D., Bronson, D., Goss, P.E., and Hogg, D. 1995. Loss of heterozygosity of tumor suppressor genes in testis cancer. Cancer Res., 55:2871-2875.
