isolation-characterization-patient-derived-pancreatic-ductal

Isolation and Characterization of Patient-derived Pancreatic Ductal Adenocarcinoma Organoid Models

Pancreatic ductal adenocarcinoma (PDAC) is amongst the most lethal malignancies. Recently, next-generation organoid culture methods enabling the ...

University of California San Diego

Malignant mesothelioma (MM) arises from mesothelial cells that line the pleural, peritoneal and pericardial surfaces. The majority of MMs are pleural and have been associated with asbestos exposure. Previously, pleural MMs have been genetically characterized by the loss of BAP1 (40-60%) as well as loss of NF2 (75%) and CDKN2A (60%). The rare peritoneal form of MM occurs in ~10% cases. With only ~300 cases diagnosed in the US per year, its link to asbestos exposure is not clear and its mutational landscape unknown.

BAP1 mutation is a frequent somatic event in peritoneal malignant mesothelioma.

Oncogenic mutations in KRAS, coupled with inactivation of p53, CDKN2A/p16, and SMAD4, drive progression of pancreatic ductal adenocarcinoma (PDA). Overexpression of MYC and deregulation of retinoblastoma (RB) further promote cell proliferation and make identifying a means to therapeutically alter cell-cycle control pathways in PDA a significant challenge. We previously showed that the basic helix-loop-helix transcription factor E47 induced stable growth arrest in PDA cells in vitro and in vivo. Here, we identified molecular mechanisms that underlie E47-induced growth arrest in low-passage, patient-derived primary and established PDA cell lines.

Article	Year
BAP1 mutation is a frequent somatic event in peritoneal malignant mesothelioma. Journal of translational medicine\| PubMed ID: 25889843	2015
E47 Governs the MYC-CDKN1B/p27-RB Network to Growth Arrest PDA Cells Independent of CDKN2A/p16 and Wild-Type p53. Cellular and molecular gastroenterology and hepatology\| PubMed ID: 30003124	2018

Randall French

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