RNA Sequencing of the NCI-60: Integration into CellMiner and CellMiner CDB.


Journal

Cancer research
ISSN: 1538-7445
Titre abrégé: Cancer Res
Pays: United States
ID NLM: 2984705R

Informations de publication

Date de publication:
01 07 2019
Historique:
received: 03 07 2018
revised: 15 02 2019
accepted: 15 05 2019
pubmed: 23 5 2019
medline: 9 4 2020
entrez: 23 5 2019
Statut: ppublish

Résumé

CellMiner (http://discover.nci.nih.gov/cellminer) and CellMinerCDB (https://discover.nci.nih.gov/cellminercdb/) are web-based applications for mining publicly available genomic, molecular, and pharmacologic datasets of human cancer cell lines including the NCI-60, Cancer Cell Line Encyclopedia, Genomics of Drug Sensitivity in Cancer, Cancer Therapeutics Response Portal, NCI/DTP small cell lung cancer, and NCI Almanac cell line sets. Here, we introduce our RNA sequencing (RNA-seq) data for the NCI-60 and their access and integration with the other databases. Correlation to transcript microarray expression levels for identical genes and identical cell lines across CellMinerCDB demonstrates the high quality of these new RNA-seq data. We provide composite and isoform transcript expression data and demonstrate diversity in isoform composition for individual cancer- and pharmacologically relevant genes, including HRAS, PTEN, EGFR, RAD51, ALKBH2, BRCA1, ERBB2, TP53, FGFR2, and CTNND1. We reveal cell-specific differences in the overall levels of isoforms and show their linkage to expression of RNA processing and splicing genes as well as resultant alterations in cancer and pharmacologic gene sets. Gene-drug pairings linked by pathways or functions show specific correlations to isoforms compared with composite gene expression, including ALKBH2-benzaldehyde, AKT3-vandetanib, BCR-imatinib, CDK1 and 20-palbociclib, CASP1-imexon, and FGFR3-pazopanib. Loss of MUC1 20 amino acid variable number tandem repeats, which is used to elicit immune response, and the presence of the androgen receptor AR-V4 and -V7 isoforms in all NCI-60 tissue of origin types demonstrate translational relevance. In summary, we introduce RNA-seq data to our CellMiner and CellMinerCDB web applications, allowing their exploration for both research and translational purposes. SIGNIFICANCE: The current study provides RNA sequencing data for the NCI-60 cell lines made accessible through both CellMiner and CellMinerCDB and is an important pharmacogenomics resource for the field.

Identifiants

pubmed: 31113817
pii: 0008-5472.CAN-18-2047
doi: 10.1158/0008-5472.CAN-18-2047
pmc: PMC6615556
mid: NIHMS1530136
doi:

Substances chimiques

Antineoplastic Agents 0

Types de publication

Journal Article Research Support, N.I.H., Intramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

3514-3524

Subventions

Organisme : Intramural NIH HHS
ID : ZIC BC011475-01
Pays : United States

Informations de copyright

©2019 American Association for Cancer Research.

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Auteurs

William C Reinhold (WC)

Developmental Therapeutic Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland. wcr@mail.nih.gov pommier@nih.gov.

Sudhir Varma (S)

Developmental Therapeutic Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
HiThru Analytics LLC, Princeton, New Jersey.

Margot Sunshine (M)

Developmental Therapeutic Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
General Dynamics Information Technology, Falls Church, Virginia.

Fathi Elloumi (F)

Developmental Therapeutic Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
General Dynamics Information Technology, Falls Church, Virginia.

Kwabena Ofori-Atta (K)

Massachusetts Institute of Technology, Computer Science and Molecular Biology, Cambridge, Massachusetts.

Sunmin Lee (S)

Developmental Therapeutic Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.

Jane B Trepel (JB)

Developmental Therapeutic Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.

Paul S Meltzer (PS)

Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.

James H Doroshow (JH)

Developmental Therapeutic Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.

Yves Pommier (Y)

Developmental Therapeutic Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland. wcr@mail.nih.gov pommier@nih.gov.

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Classifications MeSH