EGAGenomicsNextSeq 500, ILLUMINAOtherhttps://ega-archive.org/studies/EGAS00001002684EGAEGA study EGAS00001002684RNA sequencing of multiple tumor biopsies and patient-derived spheroids from five colorectal cancer patients (BAM files)Whole exome Sequencing (WES) of multiple tumor biopsies, patient-derived spheroids and leukocyte DNA from colorectal cancer patients (BAM files)Somatic mutation analysis based on Whole exome Sequencing (WES) of multiple tumor biopsies, patient-derived spheroids and leukocyte DNA from colorectal cancer patients (vcf files)restrictedEGAColorectal Tumors, Carcinomas, large bowel cancer, Colorectal Neoplasm, Carcinoma, Colorectal Cancer, Neoplasms, susceptibility to, Colorectal Carcinoma, familial, Colorectal Carcinomas, patient, Cancers, Tumor, Colorectal Tumor, cancer of large bowel, autosomal dominant, large intestine cancer, genetic, cancer of the large intestine, Colorectal, colorectal cancer, colon cancer, Client., Patient, Clients, heterogeneity, Neoplasm, cancer of the large bowel, inherited genetic, CRC, Colorectal Cancers, cancer of large intestine, constitutitional genetic, hereditary, somatic mutation, colorectal (colon or rectal) cancer, Tumors, CancerColorectal Neoplasm, Ribonucleic, D-APC1, D-APC2, Node, RNA Sequence Determination, Product, Daxin, Sequence Determination, RNA Sequence, apc, Profiles, Tumor, F20O9_210, Tp53, Long Term, Mutations, ras, PPP1R46, d-axin, bbl, Pharmaceutical Product, Min, Whole Transcriptome, Transcriptome Sequencing, GSK3beta, cytopathology, Analysis, CG1451, C-K-RAS, Effect, Non Polyadenylated, k-ras, RNA Gene Products, Atf4, Lymph, rask2, Colorectal Tumors, 929, DmelCG8669, treatment, thymus nucleic acid, Biopsies, BCC7, Analyses, Determination, Complete Exome Sequencing, Whole Transcriptome Sequencing, F20O9.210, Colorectal Carcinomas, mAPC, CRUCIFERIN C, purification, Colorectal Tumor, Sequence Determinations, large intestine cancer, AI047805, genetic, isolation and purification, medicine, Pharmaceutical, disease management, cyclosome, Therapies, Genetic Profiles, Malignancies, Double-Stranded DNA, Genotype Profiles, deoxyribonucleic acids, DNAn, Long-Term Effects, somatic mutation, colorectal (colon or rectal) cancer, Tumors, Therapy, DmelCG1451, dApc2, Carcinoma, din, l(3)S044230, ribose nucleic acid, Ki-ras, lymphatic system, DP2.5, potp, Exome, ribonucleic acids, familial, Longterm Effect, Double-Stranded, d-APC, Determinations, APC2, (Deoxyribonucleotide)n+m, Apc1, APC1, xapc, Genotype Profile, Benign, E-APC dAPC2, Genotype, Ribonukleinsaeure, apc 1, p21, apc1, pentosenucleic acids, apc2, Ribonucleic acids, bfy, Pharmaceutic, Colorectal Cancers, l(2)crc, desoxyribose nucleic acid, anon-EST:fe3D7, dAPC2, dAPC1, Carcinomas, Acid, Complete Transcriptome, cruciferin 3, histopathology, susceptibility to, 0442/30, Benign Neoplasms, AW124434, cancer of large bowel, Treatments, Dm APC2, Dm APC1, Malignant Neoplasms, ATF-4, Patient, RASK2, GS, ds DNA, Nodes, Whole Exome Sequencing, P53, cancer of the large bowel, p44, CG8669, bhy, inherited genetic, cancer of large intestine, DNA, mKIAA0147, ATF4/crc, anaphase promoting complex, other neoplasm, Transcriptome Sequencings, AI118201, CRCS, KI-RAS, D-Axin, Colorectal Cancer, Clr, DNS, e-apc, (Deoxyribonucleotide)n, Complete Exome, Effects, Neoplasms, Kras2, NS3, p53, Benign Neoplasm, number, axn, Malignant, LFS1, autosomal dominant, presence, Deoxyribonucleic acids, Colorectal, colorectal cancer, DP3, DP2, dATF-4, Deoxyribonucleic Acid, isolation, DAPC, CG6193, Gene Products, Kras-2, anon-EST:Liang-2.17, BTPS2, anon-EST:Liang-2.11, clone 2.11, D-APC, dApc, dAPC, KRAS2, KRAS1, p21B, Drugs, study, WES, Complete, Exome Sequencings, Genetic, Malignancy, Longterm, clone 2.17, Profile, K-RAS4B, K-RAS4A, Scrb1, CG9429, Double Stranded, Deoxyribonucleic acid, clumped, Ire1, Long-Term, Sequencing, CG7926, cancer of the large intestine, Non-Polyadenylated RNA, Neoplasias, Whole Exome, dAPC2/E-APC, Trp53, drugs, clustered, Pharmaceuticals., RNA Sequence Analyses, Clients, vartul, Whole, heterogeneity, RNA Sequencing, Long-Term Effect, (Deoxyribonucleotide)m, TRP53, Preparation, constitutitional genetic, DmelCG6193, Cancer, Sequence Analyses, dAxin, Products, RNA, data, Malignant Neoplasm, Complete Exome Sequencings, RNA Sequence Determinations, E-APC, K-RAS2B, SCRIB1, DNAn+1, K-RAS2A, drug, K-ras, RNS, eth, c-Ki-ras, Client, Xp53, dAXIN, Exome Sequencing, count in organism, yeast nucleic acid, Long Term Effects, Neoplasm, axin, CRC, Crc, ds-DNA, AI929937, d-APC2, nodus lymphaticus, large bowel cancer, AU020952, ribonucleic acid, NS, Complete Transcriptome Sequencing, distinct, Lymph Node, Pharmaceutic Preparations, Non Polyadenylated RNA, Colorectal Carcinoma, CC1, Non-Polyadenylated, crc, patient, Cancers, CRIB, Ribonucleic Acid, DAxin, Longterm Effects, Drug, DmelCG9429, crt, Lymph node, Preparations, colon cancer, Therapeutic, kras, CFC2, RNA Sequence Analysis, DmelCG7926, cardinality, Desoxyribonukleinsaeure, Treatment, lymph gland, APC, biopsy, Pharmaceutical Products, hereditary, Neoplasia, Pharmaceutical PreparationfalseCharacterization of genetic intratumor heterogeneity in colorectal cancer and matching patient-derived spheroid cultures.Patient-derived in vitro cultures of colorectal cancer (CRC) may help guide treatment strategies prior to patient treatment. However, most previous studies have been performed on a single biopsy per tumor. The purpose of this study was to analyze multiple spatially distinct biopsies from CRCs and see how well intratumor heterogeneity (ITH) was recapitulated in matching patient-derived spheroids. Three to five biopsies were collected from six CRC tumors. Each biopsy was split in two; one half was used for spheroid culturing, the other half was used for direct DNA and RNA purification. For two of the patients, lymph node metastases were analyzed. Somatic mutations were called from whole exome sequencing data. Each tumor contained multiple mutations shared across all biopsies and spheroids, including major CRC drivers such as APC, KRAS, and TP53. At the same time, all tumors exhibited ITH on both mutation and copy number level. The concordance between biopsies and spheroids ranged between 40-70% for coding mutations. For three of the patients the biopsy and spheroid from matching areas clustered together, meaning that the spheroid resembled the area of origin more than the other areas. However, all biopsies and spheroids contained private mutations. Thereby, multiple cultures from spatially distinct sites of the tumor increase the insight into the genetic profile of the entire tumor. RNA sequencing based molecular subtyping was stable and seemed independent of genetic ITH. In conclusion, all examined CRC tumors contained genetic ITH on mutation and copy number level. Spheroid cultures partly reflected this ITH, meaning that multiple cultures from distinct sites of the tumor improved the representation of the different genetic subclones in the primary tumor. This should be taken in to account when establishing patient-derived models for drug screening.2017-12-20 16:50:51EGAS000010026849606EGAD00001003821EGAD00001003823EGAD00001003820EGAC00001000145