Paul Scheet, PhD faculty recruitment seminar

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Paul Scheet, PhD

The cancer center welcomes Paul Scheet, PhD, from the department of epidemiology, MD Anderson Cancer Center as he presents “Surveys of Subtle Allelic Imbalance in Normal and Premalignant Tissues: Insights into Early Disease Pathology”.

Abstract: Somatically-acquired allelic imbalance (AI) is an established factor in cancer initiation and has recently been implicated as a marker for cancer risk. While DNA microarrays and next-generation sequencing are effective for whole-genome profiling of AI, 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 and diagnostics, since often for such applications the samples of interest will be comprised of heterogeneous mixtures of cells with a large component of DNA from normal (i.e. representing the germline) rather than aberrant (e.g. the tumor) sources. Here we characterize AI in several difficult settings using a powerful haplotype-based computational technique (Vattathil & Scheet, 2013, Gen Res). We first show our approach identifies different subtle mutations than have been annotated by TCGA. We then turn to a reanalysis of over 35,000 samples of healthy tissue from recent genome-wide association studies and demonstrate a 3-fold higher rate of somatic mosaicism (within-individual genomic heterogeneity), which may indicate a wider applicability for the use of mosaicism as a biomarker and yields insights on background mutation rates. We next examine premalignant tissues, profiling polyps from individuals at risk for colorectal cancer and skin cancer patients to show subtle levels of AI across critical regions of the genome; we also demonstrate extensive mosaicism in the lung field (normal-appearing tissue surrounding the tumor), consistent with recent studies of expression (Kadara et. al., 2014, JNCI). Finally, we examine lymph node tissue (of lung cancer patients) and discover chromosomal aberrations in samples that were deemed negative by pathology review but that were ultimately determined to be positive following surgical extraction, thus demonstrating potential for molecular diagnostics.

 

November 5, 2015 

2:00 – 3:00 pm

Light Refreshments Provided

Academic Office 1 

Room 7000

Contact: Cathy Van Tassel cathy.vantassel@ucdenver.edu x49566

About the author: Taylor Abarca

Taylor Abarca (Bakemeyer) is the Social Media Web Specialist at the University of Colorado Cancer Center. Contact her at Taylor.Bakemeyer [at] ucdenver.edu.

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