EGAGenomicsIllumina HiSeq 2000, ILLUMINAOtherhttps://ega-archive.org/studies/EGAS00001002717EGAEGA study EGAS00001002717Hipo-032 Metastasome of Colorectal CancerEGArestrictedColorectal Tumors, Carcinomas, large bowel cancer, treatment, Therapy, Colorectal Neoplasm, Carcinoma, tumor cell migration, Colorectal Cancer, Metastasis, Neoplasms, susceptibility to, Metastases, Colorectal Carcinoma, Colorectal Carcinomas, metastasis, Neoplasm Metastases, Cancers, neoplasm metastasis, Tumor, Colorectal Tumor, cancer of large bowel, autosomal dominant, Treatments, large intestine cancer, cancer metastasis, cancer of the large intestine, Metastase, Colorectal, colorectal cancer, disease management., colon cancer, Therapeutic, Neoplasm, Therapies, cancer of the large bowel, Treatment, CRC, Colorectal Cancers, cancer of large intestine, tumor metastasis, somatic mutation, colorectal (colon or rectal) cancer, Tumors, CancerColorectal Neoplasm, Materials, AU023367, determination, Metastasis, supply, Neoplasm Metastases, protein, neoplasm metastasis, Tumor, cancer metastasis, 1B1, Mutations, Small, anon-EST:Posey9, Readability, PHPVAR, Extracellular Matrices, protein aggregate, Colorectal Tumors, treatment, Small Temporal, Man (Taxonomy), Colorectal Carcinomas, miRNA, Primary miRNA, Colorectal Tumor, INSDC_feature:ncRNA, pri-miRNA, large intestine cancer, genetic, Adhesions, Math5, malignant neoplasm, signaling process, Adhesion, disease management, Therapies, Malignancies, l(2)01103, Nucleotide, somatic mutation, HtsF, single organism signaling, colorectal (colon or rectal) cancer, Tumors, Add, Therapy, ADD, Carcinoma, mutagenesis, Modern, frequency, familial, incomplete, Small Temporal RNA, Dmel_CG9325, results, Programs, add, abolished, Benign, htsRC, CG43443, Genetic Materials, Colorectal Cancers, pre-miRNA, Genetic Material, activation, region, nucleotides, pri miRNA, Carcinomas, miRNAs, HTS, Hts, l(2)k06121, Micro, GLI3FL, AI854843, susceptibility to, add-like, Benign Neoplasms, common, whole genome, surveillance, Pdn, Treatments, cancer of large bowel, morbidity, human, Malignant Neoplasms, metastatic, Adducin, Material, cancer of the large bowel, Cistron, MicroRNA, inherited genetic, cancer of large intestine, other neoplasm, ADD-87, biological signaling, human being, Colorectal Cancer, Neoplasms, stRNA, Ovhts, Benign Neoplasm, number, Matrix, Gene, HtsRC, CG9325, protein-containing complex, Matrices, Malignant, presence, autosomal dominant, Xt, Human, Colorectal, colorectal cancer, Homo sapiens, Add-hts, Gene Products, l(2)k14523, l(2)00634, single organism cell adhesion, Ovhts-RC, Man, study, tumor cell migration, matrisome, HTS-R1, Genetic, Malignancy, occurrence, distribution, cell adhesion molecule activity, prevalence, HTS-RC, metastasis, RNANC, cancer of the large intestine, Neoplasias, Extracellular, site, constitutitional genetic, CG34197, tumor metastasis, pre miRNA, incidence, Cancer, DmelCG43443, Hts-RC, RNA, Malignant Neoplasm, protein complex, Metastases, Proteins, Primary, Cistrons, Cell, Metastase, count in organism, disease management., MT, Micro RNA, native protein, GLI3-190, Protein, chemical analysis, Neoplasm, Mutageneses, bHLHa13, Dmel_CG34197, CRC, supply and distribution, outbreaks, Bph, large bowel cancer, primary cancer, Temporal RNA, adducin, Colorectal Carcinoma, INSDC_qualifier:other, Primary MicroRNA, Cell Adhesions, Cancers, Understanding, NCRNA, malignant tumor, endemics, signalling, Protein Gene Products, Gene Proteins, colon cancer, signalling process, Therapeutic, Modern Man, cardinality, Treatment, epidemics, assay, Attention Deficit Hyperactivity Disorder, EST D, hereditary, Neoplasia, hypothesisfalseDefining the metastasome in colorectal cancer: Implications for hypotheses on metastasis evolution and personalized therapy (HIPO-032)Personalized cancer therapy aims at individual genetic changes characterizing primary cancers. Still, however, metastasis is the major clinically unmet problem, also due to an incomplete understanding of its molecular evolution.This study is the first to define the metastasis-specific whole genome landscape of human colorectal primary vs. matched metastatic lesions.Protein coding, ncRNA genes and 3’UTRs harbored about a third each of single nucleotide variations (SNVs)/indels, 19% of them being metastasis-specific. We found novel mutational hills among ncRNAs and 3’UTRs, copy number changes able to explain changes in microRNA expression in metastases, and novel metastasis-specific mutations in the 3’UTRs on important cancer signalling genes. Some metastatic lesions showed targetable mutations not detected in the primaries. Analysis of mutual exclusivity patterns supported a model that has progressive alterations in important colorectal cancer genes and revealed new partners. Metastatic lesions were enriched in SNVs, specific structural variations, and alterations in genes affecting cell adhesion and extracellular matrix interaction.Furthermore, a hepatic stellate activation cascade was enriched in metastases, suggesting genetic programs for site-specific colonization. Allele frequency distribution and mutational signature analysis suggests a common ancestor clone to both the primary tumor and the metastasis, with additional mutagenesis ongoing in both sites independently. Taken together, our results significantly add to hypothesis generation on metastasis evolution, and suggest novel metastasis-specific genomic changes which would be missed by current personalized therapy concepts. (HIPO-032)2019-08-15 10:00:33EGAS000010027179606EGAD00001003965EGAC00001000452