Rxivist combines preprints from bioRxiv with data from Twitter to help you find the papers being discussed in your field. Currently indexing 70,242 bioRxiv papers from 306,709 authors.
The Genetic Basis of Transcriptional and Spatial Heterogeneity of Basal-Like Features in Pancreatic Ductal Adenocarcinoma
Alvin P. Makohon-Moore,
Marc A Attiyeh,
Zachary A Kohutek,
Laura D. Wood,
Ralph H. Hruban,
Gouri J Nanjangud,
David S Klimstra,
Christine A. Iacobuzio-Donahue
Posted 14 Feb 2019
bioRxiv DOI: 10.1101/548354
Posted 14 Feb 2019
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/squamous and classical/glandular morphology, phylogenetic studies revealed that squamous morphology represented a subclonal population. Cancers with squamous features were significantly more likely to have truncal 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.
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