Data from A Comprehensive PDX Gastric Cancer Collection Captures Cancer Cell–Intrinsic Transcriptional MSI Traits

• DOI: 10.1158/0008-5472.c.6511170
• Publication Date: 2023-03-31T05:13:58Z
• Authors: Simona Corso; Claudio Isella; Sara E. Bellomo; Maria Apicella; Stefania Durando; Cristina Migliore; Stefano Ughetto; Laura D’Errico; Silvia Menegon; Daniel Moya-Rull; Marilisa Cargnelutti; Tânia Capelôa; Daniela Conticelli; Jessica Giordano; Tiziana Venesio; Antonella Balsamo; Caterina Marchiò; Maurizio Degiuli; Rossella Reddavid; Uberto Fumagalli; Stefano De Pascale; Giovanni Sgroi; Emanuele Rausa; Gian Luca Baiocchi; Sarah Molfino; Filippo Pietrantonio; Federica Morano; Salvatore Siena; Andrea Sartore-Bi...; Maria Bencivenga; Valentina Mengardo; Riccardo Rosati; Daniele Marrelli; Paolo Morgagni; Stefano Rausei; Giovanni Pallabazzer; Michele De Simone; Dario Ribero; Silvia Marsoni; Antonino Sottile; Enzo Medico; Paola Cassoni; Anna Sapino; Eirini Pectasides; Aaron R. Thorner; Anwesha Nag; Samantha D. Drinan; Bruce M. Wollison; Adam J. Bass; Silvia Giordano
• Keywords: Microsatellite Instability; Druggability

<div>Abstract<p>Gastric cancer is the world's third leading cause of mortality. In spite significant therapeutic improvements, clinical outcome for patients with advanced gastric poor; thus, identification and validation novel targets extremely important from a point view. We generated wide, multilevel platform models, comprising 100 patient-derived xenografts (PDX), primary cell lines, organoids. Samples were classified according to their histology, microsatellite stability, Epstein–Barr virus status, molecular profile. This PDX widest in an academic institution, it includes all histologic types identified by The Cancer Genome Atlas. histopathologic features consistent those patients' tumors maintained throughout passages mice. Factors modulating grafting rate TNM stage, copy number gain tyrosine kinases/<i>KRAS</i> genes, stability status. PDX-derived cells/organoids demonstrated potential usefulness study targeted therapy response. Finally, transcriptomic analysis cell–intrinsic instability (MSI) signature, which was efficiently exported cancer, allowing identification, among stable (MSS) patients, subset MSI-like common aspects better prognosis. conclusion, we wide platform, whose exploitation will help identify validate “druggable” optimize strategies. Moreover, PDXs allowed MSI recognizing MSS transcriptional traits, endowed prognosis.</p>Significance:<p>This reports identifies signature that could contribute advancement precision medicine cancer.</p></div>