Patched-Associated Tumors: Modifier Genes and Pathogenesis
February 2022
TLDR The document concludes that the development of certain tumors is influenced by genetic background and that a specific gene modification can lead to tumor regression and reduced growth.
The document discusses the role of the Patched (Ptch) gene in the development of tumors such as basal cell carcinoma (BCC), medulloblastoma (MB), and rhabdomyosarcoma (RMS) and the identification of genetic modifiers that influence tumor susceptibility. It was found that the Ptchneo67/+ mice's susceptibility to these tumors depends on their genetic background, with the C57BL/6N strain being susceptible to MB and the BALB/c strain to RMS. The RMS susceptibility modifier locus Parms1 was identified on chromosome 2. However, a genetic contamination issue in the C57BL/6N strain from Charles River Laboratories led to the cancellation of the mapping project. Additionally, the document describes the creation of a conditional Ptchflox/flox mouse line, which upon Ptch deletion developed BCC and other abnormalities. BCC in these mice regressed after 200 days, showing a more differentiated phenotype with reduced proliferation, and expressed differentiation markers K1 and K10. The study also generated cell lines to further investigate Ptch function, with Ptch-/- cells showing elevated proliferation rates and both B9 and Ptch-/- cells responding to cyclopamine treatment. These findings contribute to understanding the pathogenesis of Ptch-associated tumors and may aid in developing new therapeutic approaches.
