Genomic characterization of preclinical models and intra-abdominal mucin reveal druggable targets in PMP. A, Oncoplot from exome sequencing analysis from 28 PMP-PDO or PMP-PDXO models derived from 20 patients. The most common mutated genes in all the models are presented and compared with the cohort of patients with colorectal cancer from the TCGA COADREAD, a cohort of patients with appendiceal tumors from the study of Ang and colleagues and a collection of PMP paraffin samples from the study of Alakus and colleagues. Patient and sample number, primary vs. peritoneal disease, and grade are indicated in the top. Genomic alterations are shown in different colors in the oncoplot. The percentage of PMP preclinical models with the specific mutations is indicated on the right site of the oncoplot. Finally, specific mutations in the KRAS gene are shown in the bottom site of the panel. B, ddPCR for KRASG12C using genomic DNA extracted from intra-abdominal mucin biopsy of PMP29 (sample PMP29.1; left), negative control (middle), and positive control (right). The study was performed in duplicates. Blue spots and green spots represent positive events for KRASG12C (top graph) and KRASWT genotype (bottom graph), respectively. The threshold line was determined by the control samples to separate the two clusters of negative and positive droplets. PMP, Pseudomyxoma peritonei; CRC, Colorectal cancer; PDO, Patient-derived organoid; PDXO, Patient-derived xenografts organoid; LAMN, low-grade appendiceal mucinous neoplasm; HAMN, high-grade appendiceal mucinous neoplasm; Grade 1, low-grade mucinous carcinoma peritonei; Grade 2, high-grade mucinous carcinoma peritonei; Grade 3, high-grade mucinous carcinoma peritonei with or without signet ring cells.
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Martínez‐Quintanilla et al. (2024) studied this question.
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