Project description:In this study we want present a bank of metastatic colorectal cancer (mCRC) Patient Derived Organoids (PDOs) obtained from Patient Derived Xenografts (PDXs). These models are annotated with different omics to advance our understanding of CRC. We wanted to create a resource for the scientific community to assess the predictive reliability of these preclinical models. We performed comparative analyses between PDOs and matched PDXs to assess the similarities of these two platforms regarding molecular profiles and transcriptional classification. Moreover, we analyzed how these models respond to Cetuximab, a chimeric monoclonal antibody, normally given to patients after chemotherapy, that inhibits EGFR. After having assessed models’ reliability with Cetuximab, we aimed at identifying potential synergistic drugs to individuate new possible therapeutic prospects.
Project description:To characterize metastatic progression of colorectal cancer, we performed mass spectrometry-based proteome analysis using large clinical cohort samples.
Project description:Structural rearrangements form a major class of somatic variation in cancer genomes. Local chromosome shattering, termed chromothripsis, is a mechanism proposed to be the cause of clustered chromosomal rearrangements and was recently described to occur in a small percentage of tumors. The significance of these clusters for tumor development or metastatic spread is largely unclear. We used genome-wide long mate-pair sequencing and SNP array profiling to reveal that chromothripsis is a widespread phenomenon in primary colorectal cancer and metastases. We find large and small chromothripsis events in nearly every colorectal tumor sample and show that several breakpoints of chromothripsis clusters and isolated rearrangements affect cancer genes, including NOTCH2, EXO1 and MLL3. We complemented the structural variation studies by sequencing the coding regions of a cancer exome in all colorectal tumor samples and found somatic mutations in 24 genes, including APC, KRAS, SMAD4 and PIK3CA. A pairwise comparison of somatic variations in primary and metastatic samples indicated that in many chromothripsis clusters, isolated rearrangements and point mutations are exclusively present in either the primary tumor or the metastasis and may affect cancer genes in a lesion-specific manner. We conclude that chromothripsis is a prevalent mechanism driving structural rearrangements in colorectal cancer and show that a complex interplay between point mutations, simple copy number changes and chromothripsis events drive colorectal tumor development and metastasis. We analyzed 16 tissue samples from four patients. For each patient we analyzed the DNA of a primary colon tumor sample, a normal colon tissue sample, a metastatic liver tumor sample and a normal liver tissue sample. The normal colon and normal liver samples serve as a control for the primary and metastatic tumor samples.
Project description:The goal of this experiment was to build gene expression signature associated with long-term outcomes of patients with hepatic metastatic colorectal cancer. The samples were corrected from surgically resected liver metastasis and extracted RNA was subjected to Illumina expression gene chip analysis.
Project description:To characterize metastatic progression of colorectal cancer, we performed mass spectromery-based proteome analysis using clinical samples.