Lecture Series: Paul Scheet, Ph.D "Detectable Clonal Mosaicism and Cancer Risk"

Dec 2, 2021 to Dec 2, 2021

UK College of Public Health Biostatistics and Epidemiology students and faculty are invited to this seminar featuring Paul Scheet, Ph.D. on the topic of "Detectable Clonal Mosaicism and Cancer Risk". The University of Kentucky's Markey Cancer Center is a co-host of this seminar.


Somatically-acquired mosaic copy number alterations (mCAs, i.e. chromosomal duplications, deletions or copy-neutral loss-of-heterozygosity) are established factors in cancer initiation and have recently been implicated as a marker for cancer risk (11-fold rate of increased risk for incident hematological cancers). While DNA microarrays and next-generation sequencing are effective for whole-genome profiling of mCAs, in typical settings their sensitivities become extremely limited when the aberrant cell fraction (or tumor purity) is below 10-20%.


Yet, this range may be critical for early detection, diagnostics, or studies of pre-disease tissue, since for such applications the samples of interest will be comprised of heterogeneous mixtures of cells with a substantial component of DNA from normal (i.e. representing the germline) rather than aberrant (e.g., the tumor) sources.


Here we present a haplotype-based statistical technique to powerfully detect these alterations and demonstrate its utility in challenging settings such as tumors with high stromal content, premalignant lesions, and pathologically normal tissues. Our method helped us identify samples with highly erroneous copy number calls in The Cancer Genome Atlas and we propose an automated correction for these. We also summarize mCAs in over 80,000 blood samples from genetic association studies to population rates of mosaicism, supporting the use of mCAs as biomarkers and yielding insights on background mutation patterns.


Paul Scheet, Ph.D., is Professor and Chair of the Department of Epidemiology at The University of Texas MD Anderson Cancer Center, with joint appointments in the Depts. of Genomic Medicine and Translational Molecular Pathology. A statistical geneticist with interests in complex disease and cancer genomics, Dr. Scheet serves as Leader of MD Anderson’s CCSG “Risk, Detection and Outcomes” Program.