Molecular characterization of organoids derived from pancreatic intraductal papillary mucinous neoplasms.

The Journal of Pathology
Bo HuangNicholas J Roberts

Abstract

Intraductal papillary mucinous neoplasms (IPMNs) are commonly identified non-invasive cyst-forming pancreatic neoplasms with the potential to progress into invasive pancreatic adenocarcinoma. There are few in vitro models with which to study the biology of IPMNs and their progression to invasive carcinoma. Therefore, we generated a living biobank of organoids from seven normal pancreatic ducts and ten IPMNs. We characterized eight IPMN organoid samples using whole genome sequencing and characterized five IPMN organoids and seven normal pancreatic duct organoids using transcriptome sequencing. We identified an average of 11,344 somatic mutations in the genomes of organoids derived from IPMNs, with one sample harboring 61,537 somatic mutations enriched for T→C transitions and T→A transversions. Recurrent coding somatic mutations were identified in 15 genes, including KRAS, GNAS, RNF43, PHF3, and RBM10. The most frequently mutated genes were KRAS, GNAS, and RNF43, with somatic mutations identified in six (75%), four (50%), and three (37.5%) IPMN organoid samples, respectively. On average, we identified 36 structural variants in IPMN derived organoids, and none had an unstable phenotype (> 200 structural variants). Transcriptome se...Continue Reading

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Citations

Sep 6, 2020·International Journal of Molecular Sciences·Vincenzo NascaCarmine Carbone
Oct 11, 2020·Laboratory Investigation; a Journal of Technical Methods and Pathology·Francisca BeatoJason B Fleming
Jan 26, 2021·Biotechnology Journal·Marna Eliana SakalemMiriane de Oliveira
Feb 12, 2021·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Tadasuke TsukiyamaShigetsugu Hatakeyama
Apr 23, 2021·The Journal of Pathology·Laura D Wood, Andrew J Ewald
May 29, 2021·Langenbeck's Archives of Surgery·Naziheh AssarzadeganRalph H Hruban
Jul 29, 2021·Cancer Cell International·Jia YaoXun Li

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