Uncovering the consequences of chromosome arm aneuploidies in tumorigenesis

Genetic information is carried in DNA on 46 chromosomes in each human cell. Cancer is characterized by genetic changes, including mutations in individual genes. However, more than 90% of tumors also have cells with an incorrect number of chromosomes. The exact role of these chromosome changes in tumor formation is an unanswered question in cancer biology because it is challenging to directly induce in the lab the same chromosome changes that occur in cancer. To address this, our research uses a new technology called 'CRISPR' that allows us to cut chromosomes at specific locations. With this technology, our lab is able to study the effects of specific large chromosome changes that occur in types of lung, throat, and esophageal cancers with a focus on a piece of chromosome 3. Here, our experiments will uncover the interaction between these changes and three tumor features: immune cell invasion, cancer cell evolution and tumor formation. We previously found that changes in chromosome 3 caused more immune cell invasion into a tumor. Our work here will determine how this happens and whether we can use this information to predict which patients will respond to immunotherapy. In our second aim, we will uncover how cells with these chromosome 3 changes adapt and evolve. Lastly, we will study how chromosome 3 changes affect tumor cell development and metastasis. A better understanding of how chromosomal changes affect these features of cancer will be crucial for designing new cancer treatments.