Mapping High-Resolution Genomic Alterations in Familial Adenomatous Polyposis Using Long-Read Sequencing
Nilay Sethi, MD, PhD
Assistant Professor, Dana-Farber Cancer Institute and Harvard Medical School
Associate Member, Broad Institute
Mapping High-Resolution Genomic Alterations in Familial Adenomatous Polyposis Using Long-Read Sequencing
Familial Adenomatous Polyposis (FAP) is a hereditary condition that causes individuals to develop hundreds to thousands of precancerous polyps (adenomas) in the colon, driven by inherited mutations in the APC gene. While removing the colon can prevent cancer, we still lack a clear understanding of how and why these polyps form in the first place, or why some progress to cancer while others do not. This project aims to uncover the earliest genetic changes that trigger polyp formation in people with FAP.
To do this, we are using cutting-edge long-read DNA sequencing to analyze colon organoids - miniature, lab-grown versions of colon tissue - derived from patients with FAP. These organoids faithfully replicate what happens in patients’ colons and allow us to map changes in the genome with far greater detail than ever before. This technology can detect complex genetic alterations that are often missed by standard sequencing methods.
The ultimate goal of this research is to create a comprehensive map of early disease progression in FAP, leading to new strategies for early detection, personalized risk assessment, and targeted prevention. By understanding what goes wrong before cancer begins, we hope to empower the FAP community with new tools to protect their health and prevent disease progression without invasive surgery.
