Study

Drug-perturbation-based stratification of blood cancer

Study ID Alternative Stable ID Type
EGAS00001001746 Other

Study Description

As new generations of targeted therapies emerge and tumor genome sequencing discovers increasingly comprehensive mutation repertoires, the functional relationships of mutations to tumor phenotypes remain largely unknown. Here, we measured ex vivo sensitivity of 246 blood cancers to 63 drugs alongside genome, transcriptome, and DNA methylome analysis to understand determinants of drug response. We assembled a primary blood cancer cell encyclopedia data set that revealed disease-specific sensitivities for each cancer. Within chronic lymphocytic leukemia (CLL), responses to 62% of drugs were associated with 2 or more mutations, and linked the B cell receptor (BCR) pathway to trisomy 12, an important driver of CLL. Based on drug responses, the disease could be organized into phenotypic subgroups characterized by exploitable dependencies on BCR, mTOR, or MEK signaling and associated with mutations, gene expression, and DNA methylation. Fourteen percent of CLLs were driven by mTOR signaling in a non–BCR-dependent manner. Multivariate modeling revealed immunoglobulin heavy chain variable ... (Show More)

Study Datasets 5 datasets.

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID Description Technology Samples
EGAD00001002055
Whole exome sequencing from matched tumor-control samples of 121 primary lymphoma samples. Sequencing was performed on Illumina HiSeq2000. The dataset contains FASTQ files.
Illumina HiSeq 2000 242
EGAD00001002056
Paired-end RNA sequencing using total RNA from 136 primary lymphoma samples. Sequencing was performed on the Illumina HiSeq2000 with 300bp insert size. The dataset contains FASTQ files.
Illumina HiSeq 2000 136
EGAD00010000947
Lymphoma samples using CytoSNP
Illumina CytoSNP 35
EGAD00010000948
Lymphoma samples using 450k
Illumina 450k 95
EGAD00010000949
Lymphoma samples using HumanOmni
Illumina HumanOmni2.5 104

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