Chromatin Accessibility Landscape of Human Pancreatic Ductal Adenocarcinoma (PDAC)

Therapeutic options in pancreatic ductal adenocarcinoma (PDAC) are largely limited to cytotoxic chemotherapy without the benefit of molecular markers predicting response. By ATAC-seq analyses of EpCAM+ PDAC malignant epithelial cells sorted from 54 freshly resected human tumors, we discovered a signature of 1092 chromatin loci displaying differential accessibility between patients with disease-free survival (DFS) < 1 year and patients with DFS > 1 year. Using this signature, we further develop a chromatin accessibility microarray methodology termed “ATAC-Array”, an easy-to-use platform obviating the time and cost of next-generation sequencing. PDAC prognosis can be predicted by ATAC-array, which represents a low-cost, clinically feasible technology for assessing chromatin accessibility profiles.]]>
Inclusion of Women and Minorities:
This study was open to adult women and men irrespective of age, race, or ethnicity. The participants entering this study reflect the demographics of our population and geographic areas of patients presenting to MSKCC with a tumor mass.
Inclusion Criteria:

All tumor samples were treatment-naïve surgically resected primary pancreatic ductal adenocarcinoma. Only histologically confirmed PDAC tumors were included in the study.
Age ≥ 18 years.
Able to provide written informed consent.

Exclusion Criteria:

Patients treated with neoadjuvant therapy were excluded.
Adults unable to consent.
Pregnant women.
Prisoners.

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Patient recruitment:All tissues were collected at Memorial Sloan Kettering Cancer Center (MSKCC) following a study protocol approved by the MSKCC Institutional Review Board. Informed consent was obtained from all patients. Patient samples were collected starting from Sept 2015 to March 2017 and followed until Nov 2017 for the discovery analysis, and until July 2020 for the full cohort. The study was in strict compliance with all institutional ethical regulations.]]>