- Library Home /
- Search Collections /
- Open Collections /
- Browse Collections /
- BIRS Workshop Lecture Videos /
- Integrated genomic analyses of ovarian cancer cell...
Open Collections
BIRS Workshop Lecture Videos
BIRS Workshop Lecture Videos
Integrated genomic analyses of ovarian cancer cell lines to predict drug sensitivity. Scharpf, Rob
Description
To improve our understanding of ovarian cancer, we performed genome-wide analyses of 45 ovarian cancer cell lines. Given the challenges of genomic analyses of tumors without matched normal samples, we developed approaches for detection of somatic sequence and structural changes and integrated these with epigenetic and expression alterations. Alterations not previously implicated in ovarian cancer included amplification or overexpression of ASXL1 and H3F3B, deletion or underexpression of CDC73 and TGF beta receptor pathway members, and rearrangements of YAP1-MAML2 and IKZF2-ERBB4. Dose-response analyses to targeted therapies revealed molecular dependencies, including increased sensitivity of tumors with PIK3CA and PPP2R1A alterations to PI3K inhibitor GNE-493, MYC amplifications to PARP inhibitor BMN673, and SMAD3/4 alterations to MEK inhibitor MEK162. Genome-wide rearrangements provided an improved measure of sensitivity to PARP inhibition. This study provides a comprehensive and broadly accessible resource of molecular information for development of new therapeutic avenues in ovarian cancer.
Item Metadata
Title |
Integrated genomic analyses of ovarian cancer cell lines to predict drug sensitivity.
|
Creator | |
Publisher |
Banff International Research Station for Mathematical Innovation and Discovery
|
Date Issued |
2018-11-08T15:02
|
Description |
To improve our understanding of ovarian cancer, we performed genome-wide analyses of 45 ovarian cancer cell lines. Given the challenges of genomic analyses of tumors without matched normal samples, we developed approaches for detection of somatic sequence and structural changes and integrated these with epigenetic and expression alterations. Alterations not previously implicated in ovarian cancer included amplification or overexpression of ASXL1 and H3F3B, deletion or underexpression of CDC73 and TGF beta receptor pathway members, and rearrangements of YAP1-MAML2 and IKZF2-ERBB4. Dose-response analyses to targeted therapies revealed molecular dependencies, including increased sensitivity of tumors with PIK3CA and PPP2R1A alterations to PI3K inhibitor GNE-493, MYC amplifications to PARP inhibitor BMN673, and SMAD3/4 alterations to MEK inhibitor MEK162. Genome-wide rearrangements provided an improved measure of sensitivity to PARP inhibition. This study provides a comprehensive and broadly accessible resource of molecular information for development of new therapeutic avenues in ovarian cancer.
|
Extent |
26.0
|
Subject | |
Type | |
File Format |
video/mp4
|
Language |
eng
|
Notes |
Author affiliation: Johns Hopkins University
|
Series | |
Date Available |
2019-05-08
|
Provider |
Vancouver : University of British Columbia Library
|
Rights |
Attribution-NonCommercial-NoDerivatives 4.0 International
|
DOI |
10.14288/1.0378634
|
URI | |
Affiliation | |
Peer Review Status |
Unreviewed
|
Scholarly Level |
Researcher
|
Rights URI | |
Aggregated Source Repository |
DSpace
|
Item Media
Item Citations and Data
Rights
Attribution-NonCommercial-NoDerivatives 4.0 International