Project description:Human fibroblast-derived, pluripotent cell lines are described that have normal karyotypes, express high levels of telomerase activity, and express both cell surface markers and genes that characterize human embryonic stem (ES) cells. Keywords: Induced Pluripotent Stem Cell Lines Derived from Human Somatic Cells
Project description:Solid tumors are complex organs comprising neoplastic cells and stroma, yet cancer cell lines remain widely used to study tumor biology, biomarkers and experimental therapy. Here, we performed a fully integrative analysis of global proteomic data comparing human colorectal cancer (CRC) cell lines to primary tumors and normal tissues. We found a significant, systematic difference between cell line and tumor proteomes, with a major contribution from tumor stroma proteomes. Nevertheless, cell lines overall mirrored the proteomic differences observed between tumors and normal tissues, in particular for genetic information processing and metabolic pathways, indicating that cell lines provide a system for the study of the intrinsic molecular programs in cancer cells. Intersection of cell line data with tumor data provided insights into tumor cell specific proteome alterations driven by genomic alterations. Our integration of cell line proteogenomic data with drug sensitivity data highlights the potential of proteomic data in predicting therapeutic response. We identified representative cell lines for the proteomic subtypes of primary tumors, and linked these to drug sensitivity data to identify subtype-specific drug candidates.
Project description:Chromosomal aberrations were studied both in a lung cancer cell line and colorectal cancer tumor samples. Results were verified by SKY karyotypes and by DNA ploidy analysis. The sensitivity of detecting chromosomal aberrations in tumor samples was evaluated by analyzing data from simulated mixtures of the lung cancer cell line H1395 and the normal cell line 1395BL from the same patient.
Project description:Intratumor heterogeneity is a major challenge in cancer treatment. To decipher patterns of chromosomal heterogeneity, we analyzed six colorectal cancer cell lines by multiplex interphase FISH. The mismatch repair deficient cell lines DLD-1 and HCT116 had the most stable copy numbers, whereas aneuploid cell lines displayed a higher degree of instability. We subsequently assessed the clonal evolution of a single cell in two aneuploid cell lines, SW480 and HT-29, which both have near-triploid karyotypes but different degrees of chromosomal instability. The clonal compositions of the single cell-derived daughter cell lines, as assessed by multiplex FISH, differed for HT-29 and SW480. Daughters of HT-29 were stable, clonal, and had little heterogeneity. Daughters of SW480 were more heterogeneous, with the single cell-derived daughter cell lines separating into two distinct populations with different ploidy (hyper-diploid and near-triploid), morphology, gene expression and tumorigenicity. To better understand the evolutionary trajectory for the two SW480 populations, we constructed phylogenetic trees which showed ongoing instability in the daughter cell lines.. When analyzing the evolutionary development over time, most single cell-derived daughter cell lines maintained their major clonal pattern, with the exception of one daughter of SW480 that showed a switch involving a loss of APC. Our meticulous analysis of the clonal evolution and composition of these colorectal cancer models shows that all chromosomes are subject to segregation errors, however, specific net genomic imbalances are maintained. Karyotype evolution is driven by the necessity to arrive at and maintain a specific plateau of chromosomal copy numbers as the drivers of carcinogenesis.
Project description:For the purpose of characterization of the 9p24 amplicon, we carried out high-resolution array CGH (Agilent 244K chip) analysis of four cancer cell lines, including three breast cancer cell lines, Colo824, HCC1954 and HCC70, and one esophageal cancer cell line, KYSE150.
Project description:The genomic loci with copy number alterations are known to harbor cancer genes. We investigated a comprehensive panel of gastric cancer cell lines for their genome-wide copy number alterations. Eighteen gastric cancer cell lines were profiled using Affymetrix 500K SNP arrays. For copy number calculation, seven independent normal blood samples were profiled together. The copy numbers were calculated genome-wide, in these cell lines with high resolution and reveal the cell line specific amplification and copy number changes.
Project description:The pathogenesis of paediatric central nervous system tumours is still poorly understood. In an attempt to increase the knowledge of the genetic mechanisms underlying these tumours, we performed genome-wide screening of 17 paediatric gliomas and embryonal tumours using a combination of G-band karyotyping and array comparative genomic hybridisation (aCGH). G-banding revealed abnormal karyotypes in 56% of tumour samples (9 of 16; one failed in culture), whereas aCGH analysis found copy number aberrations in all 13 tumours that could be examined. Pilocytic astrocytomas (n=3) showed normal karyotypes or simple non-recurrent translocations by karyotyping, but revealed the now well-established recurrent gain of 7q34 by aCGH. Our series included one anaplastic oligoastrocytoma, tumours that have not previously been characterised genomically in children, and an anaplastic neuroepithelial tumour (probably an oligoastrocytoma); both tumours showed losses of chromosomes 14 by G-banding as well as structural aberrations of the long arm of chromosome 6, and loss of 14q, 17p, and 22q by aCGH. Three supratentorial primitive neuroectodermal tumours (n=5) showed aberrant karyotypes; two near-diploid with mainly structural changes and one near-triploid with several trisomies including gains of one copy of chromosomes 1, 2, and 7. aCGH confirmed these findings and revealed additional recurrent gains of 1q21-44, 3p21, and 3q29. We also describe cytogenetically for the first time a cribriform neuroepithelial tumour, a recently identified variant of atypical teratoid/rhabdoid tumour with a favourable prognosis, which showed loss of 1p33, 4q13.2, 10p12.31, 10q11.22, and 22q by aCGH. Tumour sample analysed with control DNA (supplied by Agilent)
Project description:High-resolution DNA methylation array analysis of human cancer samples and normal control tissue types Analisys of Differential Methylation Regions (DMRs) of human cancer samples and normal control tissue types performing high-resolution DNA methylation array analysis
Project description:Chromosomal aberrations were studied both in a lung cancer cell line and colorectal cancer tumor samples. Results were verified by SKY karyotypes and by DNA ploidy analysis. The sensitivity of detecting chromosomal aberrations in tumor samples was evaluated by analyzing data from simulated mixtures of the lung cancer cell line H1395 and the normal cell line 1395BL from the same patient. Copy number analysis is presented on 12 colorectal cancer tumor samples and on in silico dilutions of a lung cancer cell line and its patient-matched blood cell line.