Reconstructing transposable element activity in cancer via local assembly of long reads

Transposition is a mutational process, during which DNA sequences, called transposable elements, jump or copy themselves from one location in the genome to another, producing an insertion. Such events can mediating more complex structural changes and are expected to play a significant role in cancer, with recent pan-cancer studies reporting somatic transpositions in 35% of analyzed tumors. However, most cancer genomic studies to date have relied on short-read sequencing and thus cannot comprehensively reconstruct somatic transposition events and their impact on genomic architecture. Long-read sequencing offers a promising path forward; however, even with long reads, tumor genomes are difficult to analyze due to the increased frequency and complexity of large structural changes (e.g., rearrangements and copy number changes) as well as intratumor heterogeneity, clonality, and aneuploidy. To address these challenges, this project will leverage local assembly, in conjunction with recent methodological advances for identifying transposable elements across species and calling somatic structural variants from long reads. The methods developed by this project will be used to reconstruct the landscape and history of somatic transposon activity in head-and-neck, lung, and other cancers. The successful completion of this project will provide fundamental insights into cancer progression and could lead to novel targets for diagnostics or therapy. Project Number: 1R21CA313585-01 | Fiscal Year: 2026 | NIH Institute/Center: National Cancer Institute (NCI) | Principal Investigator: Erin Molloy | Institution: UNIV OF MARYLAND, COLLEGE PARK, COLLEGE PARK, MD | Award Amount: $369,075 | Activity Code: R21 | Study Section: Special Emphasis Panel[ZRG1 BTC-T (80)] View on NIH RePORTER: https://reporter.nih.gov/project-details/11356561