Investigating aneuploidy's role in cancer cell fitness under various conditions of stress

The gain or loss of whole chromosomes, known as aneuploidy, is a distinguishing feature of cancer cells. The rapid gain or loss of hundreds of genes dramatically alters a cell's genomic landscape and is typically detrimental to cell survival under normal conditions. However, cancer cells display enhanced proliferation and overcome multiple conditions of stress, suggesting aneuploidy may increase cellular fitness. Furthermore, distinct patterns of aneuploidy are found in cancers from different anatomical sites. Despite these observations, scant research has sought to examine the role of aneuploidy in cancer, or determine whether aneuploidy is a driver or passenger mutation, or why certain aneuploidies appear to be selected for and others against. To investigate the role of aneuploidy in cancer cell fitness, we utilized the diploid colorectal cancer (CRC) cell line DLD1 and two trisomic variants carrying an extra copy of either chromosome 7 or chromosome 13, two trisomies frequently seen in colorectal cancer. To assess fitness, we compared proliferation, anchorage-independence, and invasiveness in aneuploid CRC cells versus their diploid counterpart when grown under various culture conditions, including regular media, serum-free media, cytotoxic drug-containing media, and hypoxia. We found that aneuploid cells proliferated better than diploid cells under all but standard culture conditions. Moreover, regardless of growth condition, we found that aneuploid CRC cells formed larger and more numerous colonies in soft agar (anchorage-independent growth), and displayed greater invasiveness (assessed by matrigel invasion assay). Taken together, these results indicate that aneuploidy enhances the fitness of CRC cells under stressful conditions that are likely to occur in the tumor microenvironment.

Name thesis:degree_name

Master of Science

Level thesis:degree_level

masters

Discipline thesis:degree_discipline

Biological Sciences

Department dc:contributor.department

Biological Sciences

Grantor dc:publisher

Virginia Tech

Year dc:date.issued

2015

Author dc:creator

• Rutledge, Samuel Drew

Chair dc:contributor.committeechair

• Cimini, Daniela

Committee members dc:contributor.committeemember

• Walker, Richard A.
• Hauf, Silke

• Aneuploidy
• cancer
• chromosome instability
• fitness

Statement dc:rights

• In Copyright

Licence dc:rights.uri

• http://rightsstatements.org/vocab/InC/1.0/

Dc Identifier Other

vt_gsexam:6244

OAI identifier oai:identifier

oai:vtechworks.lib.vt.edu:10919/56481