Pancreatic cancer prognosis is predicted by an ATAC-array technology for assessing chromatin accessibility

被引：24

作者：

Dhara, S. ^{[1
,2
]}

Chhangawala, S. ^{[3
,4
]}

Chintalapudi, H. ^{[1
,2
]}

Askan, G. ^{[5
]}

Aveson, V ^{[5
,6
]}

Massa, A. L. ^{[1
,2
]}

Zhang, L. ^{[5
]}

Torres, D. ^{[1
,2
]}

Makohon-Moore, A. P. ^{[5
]}

Lecomte, N. ^{[5
]}

Melchor, J. P. ^{[5
]}

Bermeo, J. ^{[5
]}

Cardenas, A. ^{[5
]}

Sinha, S. ^{[5
]}

Glassman, D. ^{[5
]}

Nicolle, R. ^{[7
]}

Moffitt, R. ^{[8
]}

Yu, K. H. ^{[5
]}

Leppanen, S. ^{[9
]}

Laderman, S. ^{[9
]}

Curry, B. ^{[9
]}

Gui, J. ^{[1
,2
]}

Balachandran, V. P. ^{[5
]}

Iacobuzio-Donahue, C. ^{[5
]}

Chandwani, R. ^{[6
]}

Leslie, C. S. ^{[4
]}

Leach, S. D. ^{[1
,2
]}

机构：

[1] Dartmouth Geisel Sch Med, Hanover, NH 03755 USA

[2] Norris Cotton Canc Ctr, Hanover, NH 08103 USA

[3] Weill Cornell Grad Sch Med Sci, New York, NY USA

[4] Mem Sloan Kettering Canc Ctr, Computat Biol Program, 1275 York Ave, New York, NY 10021 USA

[5] Mem Sloan Kettering Canc Ctr, David M Rubenstein Ctr Pancreat Canc Res, New York, NY 10021 USA

[6] Weill Cornell Med, New York, NY USA

[7] Ligue Natl Canc, Programme Cartes Identite Tumeurs, Paris, France

[8] SUNY Stony Brook, Stony Brook, NY 11794 USA

[9] Agilent Technol, Santa Clara, CA USA

来源：

NATURE COMMUNICATIONS | 2021年 / 12卷 / 01期

关键词：

TUMOR; GEMCITABINE; THERAPIES; SURVIVAL; SUBTYPES; MODELS;

D O I：

10.1038/s41467-021-23237-2

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Unlike other malignancies, therapeutic options in pancreatic ductal adenocarcinoma (PDAC) are largely limited to cytotoxic chemotherapy without the benefit of molecular markers predicting response. Here we report tumor-cell-intrinsic chromatin accessibility patterns of treatment-naive surgically resected PDAC tumors that were subsequently treated with (Gem)/Abraxane adjuvant chemotherapy. By ATAC-seq analyses of EpCAM(+) PDAC malignant epithelial cells sorted from 54 freshly resected human tumors, we show here the discovery of a signature of 1092 chromatin loci displaying differential accessibility between patients with disease free survival (DFS)<1 year and patients with DFS>1 year. Analyzing transcription factor (TF) binding motifs within these loci, we identify two TFs (ZKSCAN1 and HNF1b) displaying differential nuclear localization between patients with short vs. long DFS. 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. Applying this methodology to the original ATAC-seq libraries as well as independent libraries generated from patient-derived organoids, we validate ATAC-array technology in both the original ATAC-seq cohort as well as in an independent validation cohort. We conclude that PDAC prognosis can be predicted by ATAC-array, which represents a low-cost, clinically feasible technology for assessing chromatin accessibility profiles. ATAC-seq allows for the investigation of chromatin accessibility, a feature which can have important implications for gene regulation. Here the authors present ATAC-array to assess accessibility in human tumours and based on this predict disease prognosis.

引用

页数：9

共 35 条

[1] HTSeq-a Python']Python framework to work with high-throughput sequencing data [J].

Anders, Simon ;

Pyl, Paul Theodor ;

Huber, Wolfgang .

BIOINFORMATICS, 2015, 31 (02) :166-169

[2] Genomic analyses identify molecular subtypes of pancreatic cancer [J].

Bailey, Peter ;

Chang, David K. ;

Nones, Katia ;

Johns, Amber L. ;

Patch, Ann-Marie ;

Gingras, Marie-Claude ;

Miller, David K. ;

Christ, Angelika N. ;

Bruxner, Tim J. C. ;

Quinn, Michael C. ;

Nourse, Craig ;

Murtaugh, L. Charles ;

Harliwong, Ivon ;

Idrisoglu, Senel ;

Manning, Suzanne ;

Nourbakhsh, Ehsan ;

Wani, Shivangi ;

Fink, Lynn ;

Holmes, Oliver ;

Chin, Vencssa ;

Anderson, Matthew J. ;

Kazakoff, Stephen ;

Leonard, Conrad ;

Newell, Felicity ;

Waddell, Nick ;

Wood, Scott ;

Xu, Qinying ;

Wilson, Peter J. ;

Cloonan, Nicole ;

Kassahn, Karin S. ;

Taylor, Darrin ;

Quek, Kelly ;

Robertson, Alan ;

Pantano, Lorena ;

Mincarelli, Laura ;

Sanchez, Luis N. ;

Evers, Lisa ;

Wu, Jianmin ;

Pinese, Mark ;

Cowley, Mark J. ;

Jones, Marc D. ;

Colvin, Emily K. ;

Nagrial, Adnan M. ;

Humphrey, Emily S. ;

Chantrill, Lorraine A. ;

Mawson, Amanda ;

Humphris, Jeremy ;

Chou, Angela ;

Pajic, Marina ;

Scarlett, Christopher J. .

NATURE, 2016, 531 (7592) :47-+

[3] Identification of unique neoantigen qualities in long-term survivors of pancreatic cancer [J].

Balachandran, Vinod P. ;

Luksza, Marta ;

Zhao, Julia N. ;

Makarov, Vladimir ;

Moral, John Alec ;

Remark, Romain ;

Herbst, Brian ;

Askan, Gokce ;

Bhanot, Umesh ;

Senbabaoglu, Yasin ;

Wells, Daniel K. ;

Cary, Charles Ian Ormsby ;

Grbovic-Huezo, Olivera ;

Attiyeh, Marc ;

Medina, Benjamin ;

Zhang, Jennifer ;

Loo, Jennifer ;

Saglimbeni, Joseph ;

Abu-Akeel, Mohsen ;

Zappasodi, Roberta ;

Riaz, Nadeem ;

Smoragiewicz, Martin ;

Kelley, Z. Larkin ;

Basturk, Olca ;

Goenen, Mithat ;

Levine, Arnold J. ;

Allen, Peter J. ;

Fearon, Douglas T. ;

Merad, Miriam ;

Gnjatic, Sacha ;

Iacobuzio-Donahue, Christine A. ;

Wolchok, Jedd D. ;

DeMatteo, Ronald P. ;

Chan, Timothy A. ;

Greenbaum, Benjamin D. ;

Merghoub, Taha ;

Leach, Steven D. .

NATURE, 2017, 551 (7681) :512-+

[4] Epigenetic Therapies for Cancer [J].

Bates, Susan E. .

NEW ENGLAND JOURNAL OF MEDICINE, 2020, 383 (07) :650-663

[5] Organoid Models of Human and Mouse Ductal Pancreatic Cancer [J].

Boj, Sylvia F. ;

Hwang, Chang-Il ;

Baker, Lindsey A. ;

Chio, Iok In Christine ;

Engle, Dannielle D. ;

Corbo, Vincenzo ;

Jager, Myrthe ;

Ponz-Sarvise, Mariano ;

Tiriac, Herve ;

Spector, Mona S. ;

Gracanin, Ana ;

Oni, Tobiloba ;

Yu, Kenneth H. ;

van Boxtel, Ruben ;

Huch, Meritxell ;

Rivera, Keith D. ;

Wilson, John P. ;

Feigin, Michael E. ;

Oehlund, Daniel ;

Handly-Santana, Abram ;

Ardito-Abraham, Christine M. ;

Ludwig, Michael ;

Elyada, Ela ;

Alagesan, Brinda ;

Biffi, Giulia ;

Yordanov, Georgi N. ;

Delcuze, Bethany ;

Creighton, Brianna ;

Wright, Kevin ;

Park, Youngkyu ;

Morsink, Folkert H. M. ;

Molenaar, I. Quintus ;

Rinkes, Inne H. Borel ;

Cuppen, Edwin ;

Hao, Yuan ;

Jin, Ying ;

Nijman, Isaac J. ;

Iacobuzio-Donahue, Christine ;

Leach, Steven D. ;

Pappin, Darryl J. ;

Hammell, Molly ;

Klimstra, David S. ;

Basturk, Olca ;

Hruban, Ralph H. ;

Offerhaus, George Johan ;

Vries, Robert G. J. ;

Clevers, Hans ;

Tuveson, David A. .

CELL, 2015, 160 (1-2) :324-338

[6] Trimmomatic: a flexible trimmer for Illumina sequence data [J].

Bolger, Anthony M. ;

Lohse, Marc ;

Usadel, Bjoern .

BIOINFORMATICS, 2014, 30 (15) :2114-2120

[7]

Buenrostro JD, 2013, NAT METHODS, V10, P1213, DOI [10.1038/NMETH.2688, 10.1038/nmeth.2688]

[8] Molecular subtypes of pancreatic cancer [J].

Collisson, Eric A. ;

Bailey, Peter ;

Chang, David K. ;

Biankin, Andrew, V .

NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY, 2019, 16 (04) :207-220

[9] FOLFIRINOX or Gemcitabine as Adjuvant Therapy for Pancreatic Cancer [J].

Conroy, T. ;

Hammel, P. ;

Hebbar, M. ;

Ben Abdelghani, M. ;

Wei, A. C. ;

Raoul, J. -L. ;

Chone, L. ;

Francois, E. ;

Artru, P. ;

Biagi, J. J. ;

Lecomte, T. ;

Assenat, E. ;

Faroux, R. ;

Ychou, M. ;

Volet, J. ;

Sauvanet, A. ;

Breysacher, G. ;

Di Fiore, F. ;

Cripps, C. ;

Kavan, P. ;

Texereau, P. ;

Bouhier-Leporrier, K. ;

Khemissa-Akouz, F. ;

Legoux, J. -L. ;

Juzyna, B. ;

Gourgou, S. ;

O'Callaghan, C. J. ;

Jouffroy-Zeller, C. ;

Rat, P. ;

Malka, D. ;

Castan, F. ;

Bachet, J. -B. .

NEW ENGLAND JOURNAL OF MEDICINE, 2018, 379 (25) :2395-2406

[10] The chromatin accessibility landscape of primary human cancers [J].

Corces, M. Ryan ;

Granja, Jeffrey M. ;

Shams, Shadi ;

Louie, Bryan H. ;

Seoane, Jose A. ;

Zhou, Wanding ;

Silva, Tiago C. ;

Groeneveld, Clarice ;

Wong, Christopher K. ;

Cho, Seung Woo ;

Satpathy, Ansuman T. ;

Mumbach, Maxwell R. ;

Hoadley, Katherine A. ;

Robertson, A. Gordon ;

Sheffield, Nathan C. ;

Felau, Ina ;

Castro, Mauro A. A. ;

Berman, Benjamin P. ;

Staudt, Louis M. ;

Zenklusen, Jean C. ;

Laird, Peter W. ;

Curtis, Christina ;

Greenleaf, William J. ;

Chang, Howard Y. .

SCIENCE, 2018, 362 (6413) :420-+

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