Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A Patient-Derived Xenograft Preclinical Model for Triple Negative Breast Cancer to Evaluate PDJ Amplicon Heterogeneity and Chemotherapeutic Induction

ABSTRACT: We applied DNA content flow cytometry to ten patient derived triple negative breast cancer (TNBC) xenografts (PDXs) from the Baylor College of Medicine (BCM). We interrogated purified sorted tumor fractions from each sample with whole genome copy number variant (CNV) analyses. These identified a variety of somatic genomic lesions that are common in TNBC including three cases with 9p24.1 amplification targeting PD-L1-PDL2 and JAK2 (PDJ amplicon) and recurring focal amplicons of oncogenic drivers found commonly in the TNBC PDXs including MYC and EGFR. In addition, homozygous deletions of known tumor suppressor genes including PTEN, CDKN2A, RB1, and BRCA2, and unique targets such as CUX1 and FYN were identified. Of the three PDJ-positive amplified PDXs, 2/3 two had focal MYC amplifications and 1/3 had a RB1 homozygous deletion.

ORGANISM(S): Homo sapiens

PROVIDER: GSE151751 | GEO | 2020/06/04

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

mRNA-sequencing of breast cancer subtypes and normal tissue

Project description:Goal: To define the digital transcriptome of three breast cancer subtypes (TNBC, Non-TNBC, and HER2-positive) using RNA-sequencing technology. To elucidate differentially expressed known and novel transcripts, alternatively spliced genes and differential isoforms and lastly expressed variants in our dataset. Method: Dr. Suzanne Fuqua (Baylor College of Medicine) provided the human breast cancer tissue RNA samples. All of the human samples were used in accordance with the IRB procedures of Baylor College of Medicine. The breast tumour types, TNBC, Non-TNBC and HER2-positive, were classified on the basis of immunohistochemical and RT-qPCR classification. Results: Comparative transcriptomic analyses elucidated differentially expressed transcripts between the three breast cancer groups, identifying several new modulators of breast cancer. We discovered subtype specific differentially spliced genes and splice isoforms not previously recognized in human transcriptome. Further, we showed that exon skip and intron retention are predominant splice events in breast cancer. In addition, we found that differential expression of primary transcripts and promoter switching are significantly deregulated in breast cancer compared to normal breast. We also report novel expressed variants, allelic prevalence and abundance, and coexpression with other variation, and splicing signatures. Additionally we describe novel SNPs and INDELs in cancer relevant genes with no prior reported association of point mutations with cancer mRNA profiles of 17 breast tumor samples of three different subtypes (TNBC, non-TNBC and HER2-positive) and normal human breast organoids (epithelium) samples (NBS) were sequenced using Illumina HiSeq.

2013-11-08 | E-GEOD-52194 | biostudies-arrayexpress

Src Family Kinases as potential therapeutic targets for chemotherapy-resistant triple negative breast cancer

Project description:Here we quantified tyrosine phosphorylation (pTyr) mediated signaling networks in chemotherapy sensitive (CS) and resistant (CR) TNBC patient derived xenografts (PDX) to gain novel therapeutic insights. We identified Src Family Kinases (SFKs) as potential therapeutic targets in CR TNBC PDXs. Additionally, we performed pTyr analysis on tumor specimens derived from TNBC patients and observed lower prevalence of SFK driven tumors.

2022-10-13 | PXD034154 | Pride

mRNA-sequencing of breast cancer subtypes and normal tissue

2013-11-08 | GSE52194 | GEO

Homo sapiens

Project description:Baylor College of Medicine (BCM) Exome Sequencing of Intracranial Germ Cell Tumors

| PRJNA252892 | ENA

Genomic Landscape and Therapeutic Targets of Adenosquamous Carcinoma of the Pancreas [ATAC-seq]

Project description:We applied DNA content flow cytometry to a series of adenosquamous cancer of the pancreas (ASCP) tumor samples and patient derived xenografts (PDXs). We interrogated purified sorted tumor fractions from each sample with whole genome copy number variant (CNV) and whole exome sequencing (WES) analyses. These identified a variety of somatic genomic lesions targeting chromatin regulators in ASCP genomes that were superimposed on well characterized genomic lesions including mutations in KRAS and TP53, homozygous deletion of CDKN2A, and amplification of c-MYC, that are common in PDACs. Furthermore, a comparison of ATAC-seq profiles of ASCP and pancreatic ductal adenocarcinoma (PDAC) genomes using flow sorted PDX models distinguished genes with accessible chromatin in ASCP genomes including the lysine methyltransferase SMYD2, the pancreatic cancer stem cell driver RORγ, and a FGFR1-ERLIN2 fusion associated with focal CNVs in both genes. Organoids derived from these models were used to screen compounds of interest. Notably a FGFR inhibitor had significant activity against the FGFR1-ERLIN2 fusion positive PDX.

2020-01-14 | GSE143563 | GEO

Genomic Landscape and Therapeutic Targets of Adenosquamous Carcinoma of the Pancreas [CGH Microarray]

2020-01-08 | GSE143256 | GEO

Mus musculus

Project description:PDL2+, PDL2- and LPS treated PDL2- WT bone-marrow derived murine DCs

| PRJNA219317 | ENA

PDL2+, PDL2- and LPS treated PDL2- WT bone-marrow derived murine DCs

Project description:Cultured BMDCs were purified by FACS sorting for PDL2 surface expression and stimulated with LPS at 100 ng/mL or left unstimulated. Microarray data was used to demonstrate gene expression differences between PDL2- and PDL2+ DC populations. Microarray data was also used to show that PDL2+ mature DCs were distinct from LPS treated DCs. Two populations of murine DCs derived from ex vivo culture were compared.

2013-09-17 | E-GEOD-50898 | biostudies-arrayexpress

Epigenetic repression of STING by MYC promotes immune evasion and resistance to immune checkpoint inhibitors in triple negative breast cancer [CHIP-seq]

Project description:The MYC oncogene is frequently amplified in triple negative breast cancer (TNBC). Here, we show that MYC suppression induces immune-related hallmark gene set signatures and tumor infiltrating T cells in MYC-hyperactivated TNBCs. Mechanistically, MYC repressed stimulator of interferon genes (STING) expression via direct binding to the STING enhancer region, resulting in downregulation of the T cell chemokines CCL5, CXCL10 and CXCL11. In primary and metastatic TNBC cohorts, tumors with high MYC expression or activity exhibited low STING expression. Using a CRISPR-mediated enhancer perturbation approach, we demonstrated that MYC-driven immune evasion is mediated by STING repression. STING repression induced resistance to PD-L1 blockade in mouse models of TNBC. Finally, a small molecule inhibitor of MYC combined with PD-L1 blockade elicited a durable response in immune-cold TNBC with high MYC levels, suggesting a strategy to restore PD-L1 inhibitor sensitivity in MYC-overexpressing TNBC.

2022-03-01 | GSE196324 | GEO

Epigenetic repression of STING by MYC promotes immune evasion and resistance to immune checkpoint inhibitors in triple negative breast cancer [RNA-seq]

2022-03-01 | GSE196323 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data