A unifying paradigm for transcriptional heterogeneity and squamous features in pancreatic ductal adenocarcinoma

被引：132

作者：

Hayashi, Akimasa ^{[1
,2
]}

Fan, Jun ^{[1
,2
]}

Chen, Ruoyao ^{[3
]}

Ho, Yu-jui ^{[4
]}

Makohon-Moore, Alvin P. ^{[1
,2
]}

Lecomte, Nicolas ^{[1
,2
]}

Zhong, Yi ^{[1
,2
]}

Hong, Jungeui ^{[1
,2
]}

Huang, Jinlong ^{[1
,2
]}

Sakamoto, Hitomi ^{[1
,2
]}

Attiyeh, Marc A. ^{[1
,2
]}

Kohutek, Zachary A. ^{[1
,2
]}

Zhang, Lance ^{[1
,2
]}

Boumiza, Aida ^{[1
,2
]}

Kappagantula, Rajya ^{[1
,2
]}

Baez, Priscilla ^{[1
,2
]}

Bai, Jessica ^{[1
,2
]}

Lisi, Marta ^{[4
]}

Chadalavada, Kalyani ^{[4
]}

Melchor, Jerry P. ^{[1
,2
]}

Wong, Winston ^{[5
]}

Nanjangud, Gouri J. ^{[4
]}

Basturk, Olca ^{[6
]}

O'Reilly, Eileen M. ^{[1
,5
]}

Klimstra, David S. ^{[1
,6
]}

Hruban, Ralph H. ^{[7
]}

Wood, Laura D. ^{[7
]}

Overholtzer, Michael ^{[3
]}

Iacobuzio-Donahue, Christine A. ^{[1
,2
,6
]}

机构：

[1] Mem Sloan Kettering Canc Ctr, Sloan Kettering Inst, David M Rubenstein Ctr Pancreat Canc Res, 1275 York Ave, New York, NY 10021 USA

[2] Mem Sloan Kettering Canc Ctr, Sloan Kettering Inst, Human Oncol & Pathogenesis Program, 1275 York Ave, New York, NY 10021 USA

[3] Mem Sloan Kettering Canc Ctr, Sloan Kettering Inst, Cell Biol Program, 1275 York Ave, New York, NY 10021 USA

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

[5] Mem Sloan Kettering Canc Ctr, Dept Med, 1275 York Ave, New York, NY 10021 USA

[6] Mem Sloan Kettering Canc Ctr, Dept Pathol, 1275 York Ave, New York, NY 10021 USA

[7] Johns Hopkins Univ, Sch Med, Dept Pathol, Sol Goldman Pancreat Canc Res Ctr, Baltimore, MD 21205 USA

来源：

NATURE CANCER | 2020年 / 1卷 / 01期

基金：

美国国家卫生研究院;

关键词：

SET ENRICHMENT ANALYSIS; ADENOSQUAMOUS CARCINOMA; MUTATIONAL LANDSCAPE; CANCER; GENE; MYC; SUBTYPES; COMPETITION; METABOLISM; EXPRESSION;

D O I：

10.1038/s43018-019-0010-1

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Iacobuzio-Donahue and colleagues use integrated transcriptomic, histologic and mutational data to analyze squamous features of pancreatic ductal adenocarcinoma (PDAC), further refining the understanding of heterogeneity and evolution in PDAC. Pancreatic cancer expression profiles largely reflect a classical or basal-like phenotype. The extent to which these profiles vary within a patient is unknown. We integrated evolutionary analysis and expression profiling in multiregion-sampled metastatic pancreatic cancers, finding that squamous features are the histologic correlate of an RNA-seq-defined basal-like subtype. In patients with coexisting basal and squamous and classical and glandular morphology, phylogenetic studies revealed that squamous morphology represented a subclonal population in an otherwise classical and glandular tumor. Cancers with squamous features were significantly more likely to have clonal mutations in chromatin modifiers, intercellular heterogeneity for MYC amplification and entosis. These data provide a unifying paradigm for integrating basal-type expression profiles, squamous histology and somatic mutations in chromatin modifier genes in the context of clonal evolution of pancreatic cancer.

引用

页码：59 / +

页数：36

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