Application of Whole-Genome Sequencing in Older Esophageal Carcinoma FFPE Tissues Reveals Novel Insights

A detailed look at older formalin-fixed, paraffin-embedded tumor tissue samples using WuXi NextCODE’s SeqPlus Sequencing Methodology

Collection of fresh-frozen tumor samples is often challenging or infeasible, leading many studies to rely on formalin-fixed, paraffin-embedded (FFPE) tumor tissue samples. Because these tissues are often paired with a great deal of clinical and outcome data, analysis of these archives has the potential to lead to major advances in cancer treatment and prevention.

Whole-genome sequencing (WGS) analysis of FFPE samples could enable novel insights from these vast archival sample collections; however, robust WGS of FFPE tissues has remained elusive due to poor yields of fragmented DNA, low complexity sequencing libraries, uneven genomic coverage and sequencing artifacts attributed to fixation.

To examine WGS of stored FFPE samples, the National Cancer Institute (NCI) analyzed 20 paired esophageal carcinoma samples (primary tumors and matched germline samples) that had been stored for 10-15 years using a proprietary extraction and library preparation methodology (WuXi NextCODE’s SeqPlus). The research team assessed SeqPlus’ performance on these older FFPE tissues and measured variant call concordance between WGS and a targeted, high-depth sequencing panel (269 genes, sequenced at >400x mean coverage). SeqPlus produced consistent coverage versus the targeted panel, which showed uneven coverage across the targeted genes.

In this free webinar, participants will hear about the challenges in traditional whole-genome sequencing, WuXi NextCODE’s process for generating high-quality WGS data using FFPE samples and details of the NCI project.

Speakers

Alisa M. Goldstein, Ph.D., Principal Investigator, National Cancer Institute

Dr. Alisa Goldstein received a Ph.D. in genetic epidemiology from the University of California at Los Angeles in 1988 and subsequently joined the National Cancer Institute’s Intramural Program.  She is currently a tenured Principal Investigator in the Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics.  Dr. Goldstein completed a fellowship in the NIH InterInstitute Medical Genetics Program.  Her current research focuses on genetic epidemiologic studies of several cancers, including melanoma and upper gastrointestinal (UGI) cancer including esophageal squamous cell carcinoma, gastric cancer, and pancreatic cancer.  The main goal of her studies is to understand the role of genetic and environmental factors in the etiology of these cancers.  Her studies combine epidemiologic, genetic, genomic, clinical, and molecular methodologies.

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Shannon T. Bailey, Associate Director of Cancer Genetics, WuXi NextCODE

Dr. Shannon T. Bailey is the Associate Director of Cancer Genetics at WuXi NextCODE where he manages analysis of next-generation sequencing data. Prior to this position, he was an Instructor in Medicine at Harvard Medical School and the Dana-Farber Cancer Institute where he performed research examining the molecular mechanisms of estrogen receptor (ER)-positive breast cancer. His work has identified mechanisms underlying ER-mediated breast cancer cell survival involving transcription factor and microRNA regulation. He completed his graduate education at Yale University where he earned the degrees of M.S., M.Phil., and Ph.D. in Cellular and Molecular Physiology in the laboratory of Dr. Sankar Ghosh. Prior to his graduate studies, Dr. Bailey discovered the hormone resistin at the University of Pennsylvania Medical School in the laboratory of Dr. Mitchell Lazar, which was published in a study totaling over 2,400 citations to date. Dr. Bailey has been the recipient of numerous awards including the prestigious Ford Foundation predoctoral fellowship, the Leadership Alliance/Schering-Plough dissertation fellowship, and a postdoctoral fellowship from the Terri Broduer Research Foundation. He was also named a Minority Scholar in Cancer Research by the American Association for Cancer Research in 2010.

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