Project description:41 lung adenocarcinoma from never-smokers hybridized on Illumina SNP arrays on 13 HumanCNV370-Quadv3 chips. High-resolution array comparative genomic hybridization analysis of lung adenocarcinoma in 41 never smokers for identification of new minimal common regions (MCR) of gain or loss. The SNP array analysis validated copy-number aberrations and revealed that RB1 and WRN were altered by recurrent copy-neutral loss of heterozygosity.The present study has uncovered new aberrations containing cancer genes. The oncogene FUS is a candidate gene in the 16p region that is frequently gained in never smokers. Multiple genetic pathways defined by gains of MYC, deletions of RB1 and WRN or gains on 7p and 7q are involved in lung adenocarcinoma in never smokers. A 'Cartes d'Identite des Tumeurs' (CIT) project from the French National League Against Cancer (http://cit.ligue-cancer.net) 41 samples hybridized on Illumina SNP arrays. Submitter : Fabien PETEL petelf@ligue-cancer.net . Project leader : Pr Pierre FOURET pierre.fouret@psl.aphp.fr
Project description:Disseminated epithelial cells can be isolated from the bone marrow of a far greater frac-tion of prostate-cancer patients than the fraction of patients who progress to metastatic disease. To provide a better understanding of these cells, we have characterized their genomic altera-tions. We first present an array comparative genomic hybridization method capable of detecting genomic changes in the small number of disseminated cells (10-20) that can typically be ob-tained from bone-marrow aspirates of prostate-cancer patients. We show multiple regions of copy-number change, including alterations common in prostate cancer, such as 8p loss, 8q gain, and gain encompassing the androgen-receptor gene on Xq, in the disseminated cell pools from 11 metastatic patients. We found fewer and less striking genomic alterations in the 48 pools of disseminated cells from patients with organ-confined disease. However, we identify changes shared by these samples with their corresponding primary tumors and prostate-cancer altera-tions reported in the literature, evidence that these cells, like those in advanced disease, are disseminated tumor cells (DTCs). We also demonstrate that DTCs from patients with advanced and localized disease share several abnormalities, including losses containing cell-adhesion genes and alterations reported to associate with progressive disease. These shared alterations might confer the capability to disseminate or establish secondary disease. Overall, the spectrum of genomic deviations is evidence for metastatic capacity in advanced-disease DTCs and varia-tion in that capacity in DTCs from localized disease. Our analysis lays the foundation for eluci-dation of the relationship between DTC genomic alterations and progressive prostate cancer. Keywords: array comparative genomic hybridization, prostate cancer, disseminated cells
Project description:Gene expression profiling of immortalized human mesenchymal stem cells with hTERT/E6/E7 transfected MSCs. hTERT may change gene expression in MSCs. Goal was to determine the gene expressions of immortalized MSCs.
Project description:Tumor heterogeneity may reduce the efficacy of molecularly guided systemic therapy for cancers that have metastasized. To determine whether the genomic alterations in a single metastasis provide a reasonable assessment of the major oncogenic drivers of other dispersed metastases in an individual, we analyzed multiple tumors from men with disseminated prostate cancer through whole-exome sequencing, array comparative genomic hybridization (CGH) and RNA transcript profiling, and we compared the genomic diversity within and between individuals.
Project description:Circulating (CTCs) and disseminated (DTCs) tumor cells are of great interest to the field of cancer research as they provide a minimally-invasive window for assessing aspects of cancer biology including tumor heterogeneity, a means to discover biomarkers of disease behavior, and a way to identify and prioritize therapeutic targets in the emerging era of precision oncology. However, the rarity of CTC/DTC poses a significant challenge to the consistent success in analyzing the molecular features of these cells including genomic aberrations. Herein, we demonstrate our optimized and robust methods to reproducibly detect genomic copy number alterations in samples of 2-40 cells after whole-genome amplification using a high resolution SNP-array platform and refined computational algorithms. We have determined the limit of detection for heterogeneity within a sample as 50% and also demonstrated success in analyzing single cells. We validated the genes in genomic regions that are frequently amplified or deleted by qPCR and nCounter copy number quantification. We further applied these methods to DTCs isolated from individuals with advanced prostate cancer to confirm the highly aberrant nature of these cells. We compared copy number alterations of DTCs to matched metastatic tumors isolated from the same individual to gain biological insight. These developments provide high-resolution genomic profiling of single and rare cell populations, and should be applicable to a wide-range of sample sources.