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

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

Authors:	Hayashi, A.; Fan, J.; Chen, R.; Ho, Y. J.; Makohon-Moore, A. P.; Lecomte, N.; Zhong, Y.; Hong, J.; Huang, J.; Sakamoto, H.; Attiyeh, M. A.; Kohutek, Z. A.; Zhang, L.; Boumiza, A.; Kappagantula, R.; Baez, P.; Bai, J.; Lisi, M.; Chadalavada, K.; Melchor, J. P.; Wong, W.; Nanjangud, G. J.; Basturk, O.; O'Reilly, E. M.; Klimstra, D. S.; Hruban, R. H.; Wood, L. D.; Overholtzer, M.; Iacobuzio-Donahue, C. A.
Article Title:	A unifying paradigm for transcriptional heterogeneity and squamous features in pancreatic ductal adenocarcinoma
Abstract:	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.
Keywords:	metabolism; gene; adenosquamous carcinoma; competition; myc; expression; mutational landscape; subtypes; cancer; set enrichment analysis
Journal Title:	Nature Cancer
Volume:	1
Issue:	1
ISSN:	2662-1347
Publisher:	Nature Research
Date Published:	2020-01-01
Start Page:	59
End Page:	74
Language:	English
ACCESSION:	WOS:000610411800011
DOI:	10.1038/s43018-019-0010-1
PROVIDER:	wos
PUBMED:	35118421
PMCID:	PMC8809486
Notes:	Article -- Source: Wos