Gene amplifications in tumor cells:newly developed or adapted from normal cells?

• Applicant: Privatdozentin Dr. Ulrike Fischer
• Subject Area: Human Genetics
• Term: from 2009 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 151348859

Gene amplification is a hallmark of human tumors and has an impact on patients prognosis in several cancers. As of now, gene amplifications during normal development are only known from amphibians and flies. The data from my first grant period show that gene amplifications can also occur in normal mammalian cells. Specifically, during differentiation of human and mouse neural progenitor cells genome-wide gene amplifications were detectable. Notably, about 50% of the mouse amplified chromosome regions were also detected in human. In addition, many of these amplified chromosomal regions overlap with chromosomal regions amplified in human glioblastoma. In contrast to gene amplifications in human tumor cells, gene amplifications of human and mouse neural progenitor cells appear to occur only during a small time-window in a small number of cells. Based on these data, the following questions arise:Are gene amplifications detectable in other cells than neural stem cells during differentiation? Is there evidence for gene amplification being a frequent phenomenon during differentiation in mammalian cells? What is the fate of the amplified DNA and of the cells that harbor amplifications? What is the genomic organization of the amplified DNA in neural progenitor cells and can known models of the origin of gene amplification be supported or disproved by these genomic structures?

• DFG Programme: Research Grants
• Participating Persons: Professorin Dr. Carola Meier; Professor Dr. Jens Rettig