Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Genome-wide analysis of basal gene expression in pediatric acute lymphoblastic leukemia xenograft cells

ABSTRACT: Analysis of basal gene expression in patient-derived xenograft cells. A panel of pediatric T-, B- and MLL-ALL xenografts was utilized to further understand the biology of leukemia Total RNA was isolated from patient-derived xenograft cells. Array analysis was carried out on Illumina beadchip HT12

ORGANISM(S): Homo sapiens

SUBMITTER: Santi Suryani

PROVIDER: E-GEOD-52991 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Cell and molecular determinants of in vivo efficacy of the BH3 mimetic ABT-263 against pediatric acute lymphoblastic leukemia xenografts.

Suryani Santi S Carol Hernan H Chonghaile Triona Ni TN Frismantas Viktoras V Sarmah Chintanu C High Laura L Bornhauser Beat B Cowley Mark J MJ Szymanska Barbara B Evans Kathryn K Boehm Ingrid I Tonna Elise E Jones Luke L Manesh Donya Moradi DM Kurmasheva Raushan T RT Billups Catherine C Kaplan Warren W Letai Anthony A Bourquin Jean-Pierre JP Houghton Peter J PJ Smith Malcolm A MA Lock Richard B RB

Clinical cancer research : an official journal of the American Association for Cancer Research 20140710 17

<h4>Purpose</h4>Predictive biomarkers are required to identify patients who may benefit from the use of BH3 mimetics such as ABT-263. This study investigated the efficacy of ABT-263 against a panel of patient-derived pediatric acute lymphoblastic leukemia (ALL) xenografts and utilized cell and molecular approaches to identify biomarkers that predict in vivo ABT-263 sensitivity.<h4>Experimental design</h4>The in vivo efficacy of ABT-263 was tested against a panel of 31 patient-derived ALL xenogra ...[more]

PMID: 25013123

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Project description:The number of relevant and well-characterized cell lines and xenograft models for studying human breast cancer are few, and may represent a limitation for this field of research. With the aim of developing new breast cancer model systems for in vivo studies of hormone dependent and independent tumor growth, progression and invasion, and for in vivo experimental therapy studies, we collected primary mammary tumor specimens from patients, and implanted them in immunodeficient mice. Primary tumor tissue from 29 patients with breast cancer was implanted subcutaneously with matrigel in SCID mice, in the presence of continuous release of estradiol. The tumors were transferred into new animals when reaching a diameter of 15mm and engrafted tumors were harvested for morphological and molecular characterization from passage six. Further, gene expression profiling was performed using Agilent Human Whole Genome Oligo Microarrays, as well as DNA copy number analysis using Agilent Human Genome CGH 244K Microarrays. Of the 30 primary tumors implanted into mice (including two implants from the same patient), two gave rise to viable tumors beyond passage ten. One showed high expression levels of estrogen receptor-alpha protein (ER) while the other was negative. Histopathological evaluation of xenograft tumors was carried out at passage 10-12; both xenografts maintained the morphological characteristics of the original tumors (classified as invasive grade III ductal carcinomas). The genomic profile of the ER-positive xenograft tumor resembled the profile of the primary tumor, while the profile obtained from the ER-negative parental tumor was different from the xenograft. However, the ER-negative parental tumor and xenograft clustered on the same branch using unsupervised hierarchical clustering analysis on RNA microarray expression data of "intrinsic genes". A significant variation was observed in the expression of extracellular matrix (ECM)-related genes, which were found downregulated in the engrafted tumors compared to the primary tumor. By IHC and qRT-PCR we found that the downregulation of stroma-related genes was compensated by the overexpression of such molecules by the mouse host tissue. The two established breast cancer xenograft models showed different histopathological characteristics and profound diversity in gene expression patterns that in part can be associated to their ER status and here described as basal-like and luminal-like phenotype, respectively. These two new breast cancer xenografts represent useful preclinical tools for developing and testing of new therapies and improving our knowledge on breast cancer biology. Set of arrays organized by shared biological context, such as organism, tumors types, processes, etc.

Dataset Information

Genome-wide analysis of basal gene expression in pediatric acute lymphoblastic leukemia xenograft cells

Publications

Cell and molecular determinants of in vivo efficacy of the BH3 mimetic ABT-263 against pediatric acute lymphoblastic leukemia xenografts.

Similar Datasets

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