| Literature DB >> 35118421 |
Akimasa Hayashi1,2, Jun Fan1,2, Ruoyao Chen3, Yu-Jui Ho4, Alvin P Makohon-Moore1,2, Nicolas Lecomte1,2, Yi Zhong1,2, Jungeui Hong1,2, Jinlong Huang1,2, Hitomi Sakamoto1,2, Marc A Attiyeh1,2, Zachary A Kohutek1,2, Lance Zhang1,2, Aida Boumiza1,2, Rajya Kappagantula1,2, Priscilla Baez1,2, Jessica Bai1,2, Marta Lisi4, Kalyani Chadalavada4, Jerry P Melchor1,2, Winston Wong5, Gouri J Nanjangud4, Olca Basturk6, Eileen M O'Reilly1,5, David S Klimstra1,6, Ralph H Hruban7, Laura D Wood7, Michael Overholtzer3, Christine A Iacobuzio-Donahue8,9,10.
Abstract
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.Entities:
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Year: 2020 PMID： 35118421 PMCID： PMC8809486 DOI： 10.1038/s43018-019-0010-1
Source DB: PubMed Journal: Nat Cancer ISSN： 2662-1347