This study focuses on the whole-exome sequencing (WES) of patient-derived organoids (PDOs) established from colorectal cancer (CRC) tumors collected at Columbia University. CRC remains a major cause of cancer-related mortality due to its metastatic progression and resistance to therapy. To model CRC at the patient level, we generated 3D organoid cultures from primary and metastatic tumors, preserving their genetic and phenotypic characteristics. The study cohort consists of 9 CRC patients with microsatellite-stable adenocarcinomas from the ascending, transverse, and descending colon, as well as the rectum, with differentiation statuses ranging from well to moderate and moderate-poor. Notably, for one patient, we generated organoids from both the primary tumor and matched liver metastases, allowing for a comparative analysis of tumor evolution. PDOs were derived from these tumors and subjected to WES at early passage to profile somatic mutations, copy number variations, and other genomic alterations to identify mutational signatures. Mutations identified in the PDOs were cross-referenced and confirmed with mutational data from the Columbia Solid Tumor Panel, which was conducted on all tumor tissues prior to organoid establishment. Molecular technologies employed include next-generation sequencing (NGS) for WES, enabling high-resolution characterization of the genomic landscape of CRC PDOs. WES of PDOs allowed us to classify tumor samples based on oncogenic mutations and mutation types, with a specific focus on <a href="https://www.ncbi.nlm.nih.gov/gene/5290">PIK3CA</a>. Notably, the efficacy of PI3Kα-specific pharmacologic inhibitors in suppressing organoid growth was dependent on the mutational status of <a href="https://www.ncbi.nlm.nih.gov/gene/3845">KRAS</a> and <a href="https://www.ncbi.nlm.nih.gov/gene/5290">PIK3CA</a>, underscoring the importance of genomic context in therapeutic response. The dataset available through dbGaP includes raw WES data from CRC PDOs.

Sequencing of 3D Organoids Derived From Colorectal Cancer Patients

LIN28B-mediated PI3K/AKT pathway activation promotes metastasis in colorectal cancer models