Defining the role of aneuploidy throughout tumorigenesis

Aneuploidy is a state of genome imbalance which alters the copy number of whole chromosomes. While aneuploidy is rare in healthy tissues, it is one of the most common features of cancerous tumors. Studies of aneuploid yeast and aneuploid mammalian cells growing in culture revealed that aneuploidy induces cellular stress and slows proliferation. So it is surprising that aneuploidy is a hallmark of cancer, a disease of cellular over-proliferation and inappropriate cell survival. We sought to elucidate aneuploidy's role in tumorigenesis by defining the factors that affect the prevalence of aneuploid cells in normal, pre-cancerous, and cancerous tissues. First, we investigated whether aneuploid mammalian cells experience fitness defects in vivo. We found that aneuploidy decreases hematopoietic stem cells' fitness and that aneuploid cells are selected against in normal, regenerating tissues in vivo.

Name thesis:degree_name

Doctoral

Department dc:contributor.department

Massachusetts Institute of Technology. Department of Biology

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2021

Author dc:creator

• Silberman, Rebecca Estelle.

Advisor dc:contributor.advisor

• Angelika Amon.

• Biology.

Statement dc:rights

• MIT theses may be protected by copyright. Please reuse MIT thesis content according to the MIT Libraries Permissions Policy, which is available through the URL provided.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

https://hdl.handle.net/1721.1/130665

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/130665