ABSTRACT
Cancer cell lines are widely used as in vitro models of tumorigenesis, facilitating fundamental discoveries in cancer biology and translational medicine. Currently, there are few options for glioblastoma (GBM) treatment and limited in vitro models with accurate genomic and transcriptomic characterization. Here, a detailed characterization of a new GBM cell line, namely AHOL1, was conducted in order to fully characterize its molecular composition based on its karyotype, copy number alteration (CNA), and transcriptome profiling, followed by the validation of key elements associated with GBM tumorigenesis. Large numbers of CNAs and differentially expressed genes (DEGs) were identified. CNAs were distributed throughout the genome, including gains at Xq11.1-q28, Xp22.33-p11.1, Xq21.1-q21.33, 4p15.1-p14, 8q23.2-q23.3 and losses at Yq11.21-q12, Yp11.31-p11.2, and 15q11.1-q11.2 positions. Nine druggable genes were identified, including HCRTR2, ETV1, PTPRD, PRKX, STS, RPS6KA6, ZFY, USP9Y, and KDM5D. By integrating DEGs and CNAs, we identified 57 overlapping genes enriched in fourteen pathways. Altered expression of several cancer-related candidates found in the DEGs-CNA dataset was confirmed by RT-qPCR. Taken together, this first comprehensive genomic and transcriptomic landscape of AHOL1 provides unique resources for further studies and identifies several druggable targets that may be useful for therapeutics and biologic and molecular investigation of GBM.
Subject(s)
Glioblastoma , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , Genome , Genomics , Glioblastoma/genetics , Histone Demethylases , Humans , Minor Histocompatibility Antigens , TranscriptomeABSTRACT
Cancer cell lines are widely used as in vitro models of tumorigenesis, facilitating fundamental discoveries in cancer biology and translational medicine. Currently, there are few options for glioblastoma (GBM) treatment and limited in vitro models with accurate genomic and transcriptomic characterization. Here, a detailed characterization of a new GBM cell line, namely AHOL1, was conducted in order to fully characterize its molecular composition based on its karyotype, copy number alteration (CNA), and transcriptome profiling, followed by the validation of key elements associated with GBM tumorigenesis. Large numbers of CNAs and differentially expressed genes (DEGs) were identified. CNAs were distributed throughout the genome, including gains at Xq11.1-q28, Xp22.33-p11.1, Xq21.1-q21.33, 4p15.1-p14, 8q23.2-q23.3 and losses at Yq11.21-q12, Yp11.31-p11.2, and 15q11.1-q11.2 positions. Nine druggable genes were identified, including HCRTR2, ETV1, PTPRD, PRKX, STS, RPS6KA6, ZFY, USP9Y, and KDM5D. By integrating DEGs and CNAs, we identified 57 overlapping genes enriched in fourteen pathways. Altered expression of several cancer-related candidates found in the DEGs-CNA dataset was confirmed by RT-qPCR. Taken together, this first comprehensive genomic and transcriptomic landscape of AHOL1 provides unique resources for further studies and identifies several druggable targets that may be useful for therapeutics and biologic and molecular investigation of GBM.
Subject(s)
Humans , Glioblastoma/genetics , Gene Expression Regulation, Neoplastic , Minor Histocompatibility Antigens , Genome , Genomics , Cell Line, Tumor , Histone Demethylases , TranscriptomeABSTRACT
Para estudar a influência do processo granulomatoso esquistossomóticosobre as células ganglionares mioentéricas, foram utilizados 30 camundongos albinos Swiss infectadoscom 50 cercárias da cepa SLM do S. mansoni.O grupo controle foi constituído por dez animais näo infectados. Após sessenta dias de infecçäo, cortes histológicos do intestino delgadocorados por hematoxilina-eosina e P.A.S. demonstraram granulomas periovulares em todas as camadas da parede intestinal. Através do método imunohistoquímico indireto, usando-se a enolase neurônio-específica como marcador, observou-se desorganizaçäo do plexo mioentêrico em áreas contendo granulomas. Além disso, ocorreu rarefaçäo das estaçöes ganglionares, com aparente destruiçäo de células neuronais. A possível contribuiçäo dessas alteraçöes para a sintomatologia da esquistossomose humana é avaliada
Subject(s)
Animals , Mice , Clinical Trial , Schistosomiasis mansoni/physiopathology , Enteroendocrine Cells/physiology , Enteroendocrine Cells/parasitologyABSTRACT
Karyological characterizations of C. s. utahicki (2n = 54) and C. s. chiropotes (2n = 54) showed that these two subspecies are chromosomally very similar. In a single, isolated specimen of C s. utahicki, however, a derived, biarmed, chromosome 14 was found in the heterozygous condition. This variant chromosome was identical with pair 10 in C. s. chiropotes in which this chromosome type was apparently fixed. Chromosome differences between these subspecies might be transitional, leading to the establishment of two different karyomorphic populations derived from a once uniform karyotypic group that split into separate allopatric subspecies. © 1992 Wiley-Liss, Inc.
