Multiple ABCB1 transcriptional fusions in drug resistant high-grade serous ovarian and breast cancer View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-12

AUTHORS

Elizabeth L. Christie, Swetansu Pattnaik, Jessica Beach, Anthony Copeland, Nineveh Rashoo, Sian Fereday, Joy Hendley, Kathryn Alsop, Samuel L. Brady, Greg Lamb, Ahwan Pandey, Anna deFazio, Heather Thorne, Andrea Bild, David D. L. Bowtell

ABSTRACT

ABCB1 encodes Multidrug Resistance protein (MDR1), an ATP-binding cassette member involved in the cellular efflux of chemotherapeutic drugs. Here we report that ovarian and breast samples from chemotherapy treated patients are positive for multiple transcriptional fusions involving ABCB1, placing it under the control of a strong promoter while leaving its open reading frame intact. We identified 15 different transcriptional fusion partners involving ABCB1, as well as patients with multiple distinct fusion events. The partner gene selected depended on its structure, promoter strength, and chromosomal proximity to ABCB1. Fusion positivity was strongly associated with the number of lines of MDR1-substrate chemotherapy given. MDR1 inhibition in a fusion positive ovarian cancer cell line increased sensitivity to paclitaxel more than 50-fold. Convergent evolution of ABCB1 fusion is therefore frequent in chemotherapy resistant recurrent ovarian cancer. As most currently approved PARP inhibitors (PARPi) are MDR1 substrates, prior chemotherapy may precondition resistance to PARPi. More... »

PAGES

1295

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41467-019-09312-9

DOI

http://dx.doi.org/10.1038/s41467-019-09312-9

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1112880978

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30894541


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Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/s41467-019-09312-9'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/s41467-019-09312-9'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/s41467-019-09312-9'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/s41467-019-09312-9'


 

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