American Association for Cancer Research
00085472can200078-sup-235227_3_supp_6429093_qdj3g4.docx (14.84 kB)

Table S2 from Genomic and Epigenomic Landscaping Defines New Therapeutic Targets for Adenosquamous Carcinoma of the Pancreas

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journal contribution
posted on 2023-03-31, 04:01 authored by Elizabeth Lenkiewicz, Smriti Malasi, Tara L. Hogenson, Luis F. Flores, Whitney Barham, William J. Phillips, Alexander S. Roesler, Kendall R. Chambers, Nirakar Rajbhandari, Akimasa Hayashi, Corina E. Antal, Michael Downes, Paul M. Grandgenett, Michael A. Hollingsworth, Derek Cridebring, Yuning Xiong, Jeong-Heon Lee, Zhenqing Ye, Huihuang Yan, Matthew C. Hernandez, Jennifer L. Leiting, Ronald M. Evans, Tamas Ordog, Mark J. Truty, Mitesh J. Borad, Tannishtha Reya, Daniel D. Von Hoff, Martin E. Fernandez-Zapico, Michael T. Barrett

Evidence-based variant categorization


Lee Hanley Foundation and a Stand up to Cancer

Lustgarten-Cancer Research UK

Pancreatic Cancer Dream Team Research


Lustgarten Foundation and Stand Up To Cancer

Tobacco Related Disease Research Program

NCI Cancer Center Support grant

SPORE in 19 Pancreatic Cancer

Pancreatic Cancer Detection Consortium

National Cancer Institute

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NCI Research Specialist



Adenosquamous cancer of the pancreas (ASCP) is a subtype of pancreatic cancer that has a worse prognosis and greater metastatic potential than the more common pancreatic ductal adenocarcinoma (PDAC) subtype. To distinguish the genomic landscape of ASCP and identify actionable targets for this lethal cancer, we applied DNA content flow cytometry to a series of 15 tumor samples including five patient-derived xenografts (PDX). We interrogated purified sorted tumor fractions from these samples with whole-genome copy-number variant (CNV), whole-exome sequencing, and Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) analyses. These identified a variety of somatic genomic lesions targeting chromatin regulators in ASCP genomes that were superimposed on well-characterized genomic lesions including mutations in TP53 (87%) and KRAS (73%), amplification of MYC (47%), and homozygous deletion of CDKN2A (40%) that are common in PDACs. Furthermore, a comparison of ATAC-seq profiles of three ASCP and three PDAC genomes using flow-sorted PDX models identified genes with accessible chromatin unique to the ASCP genomes, including the lysine methyltransferase SMYD2 and the pancreatic cancer stem cell regulator RORC in all three ASCPs, and a FGFR1-ERLIN2 fusion associated with focal CNVs in both genes in a single ASCP. Finally, we demonstrate significant activity of a pan FGFR inhibitor against organoids derived from the FGFR1-ERLIN2 fusion–positive ASCP PDX model. Our results suggest that the genomic and epigenomic landscape of ASCP provide new strategies for targeting this aggressive subtype of pancreatic cancer. These data provide a unique description of the ASCP genomic and epigenomic landscape and identify candidate therapeutic targets for this dismal cancer.

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