My laboratory studies the way human mobile elements contribute to insertional mutagenesis and recombination in cancer, and the influences of DNA repair deficiencies.
Genetic instability is one of the most critical contributors to cancer. Human mobile elements have the potential to contribute to genetic instability both because of their capability of insertional mutagenesis as well as their presence as repetitive DNA sequences in the genome that can contribute to mutagenic recombination events. Both of these processes a greatly stimulated, but to variable extents, in different tumors. We have studied the epigenetic mechanisms that control the expression of a small number of the 500,000 L1 elements that are active in any given tumor type. Our data support the likelihood that there are typically only one or two potentially active L1 loci expressed in any given tumor and that the exact loci are different between tumors, as well as polymorphic between individuals. We are working on a study to determine whether individual loci may serve as ‘risk’ loci for cancer incidence or progression, particularly in prostate cancer.
We have also developed a reporter assay to measure the influence of Alu elements on the recombination process. We have shown that the relative amount of this recombination, as well as the specific mechanism and products formed, differs between different tumors. This is largely dependent on the nature of the underlying DNA repair defects in the tumors. Our studies are beginning to lay the framework for understanding these forms of instability in response to various environmental insults and interns of forming different types of mutagenic footprints.
ORCID ID: 0000-0002-1067-3028
Hum Mutat. 2021 May;42(5):600-613. doi: 10.1002/humu.24193. Epub2021 Mar 19.
Keywords: genetic instability; Retroelements; mobile elements; DNA repair; insertional mutagenesis; recombination;