Journal article

LRP1B Deletion in High-Grade Serous Ovarian Cancers Is Associated with Acquired Chemotherapy Resistance to Liposomal Doxorubicin

Prue A Cowin, Joshy George, Sian Fereday, Elizabeth Loehrer, Peter Van Loo, Carleen Cullinane, Dariush Etemadmoghadam, Sarah Ftouni, Laura Galletta, Michael S Anglesio, Joy Hendley, Leanne Bowes, Karen E Sheppard, Elizabeth L Christie, Richard B Pearson, Paul R Harnett, Viola Heinzelmann-Schwarz, Michael Friedlander, Orla McNally, Michael Quinn Show all

CANCER RESEARCH | AMER ASSOC CANCER RESEARCH | Published : 2012

Abstract

High-grade serous cancer (HGSC), the most common subtype of ovarian cancer, often becomes resistant to chemotherapy, leading to poor patient outcomes. Intratumoral heterogeneity occurs in nearly all solid cancers, including ovarian cancer, contributing to the development of resistance mechanisms. In this study, we examined the spatial and temporal genomic variation in HGSC using high-resolution single-nucleotide polymorphism arrays. Multiple metastatic lesions from individual patients were analyzed along with 22 paired pretreatment and posttreatment samples. We documented regions of differential DNA copy number between multiple tumor biopsies that correlated with altered expression of genes ..

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Grants

Awarded by U.S. Army Medical Research and Materiel Command


Awarded by National Health and Medical Research Council of Australia (NHMRC)


Awarded by NHMRC


Awarded by Worldwide Cancer Research


Funding Acknowledgements

This work has been supported by an Association for International Cancer Research (AICR) grant (P. A. Cowin, D. D. L. Bowtell). AOCS was supported by the U.S. Army Medical Research and Materiel Command under DAMD17-01-1-0729, the National Health and Medical Research Council of Australia (NHMRC, 400281 & 400413), Cancer Council Victoria, Cancer Council Queensland, Cancer Council New South Wales, Cancer Council South Australia, The Cancer Foundation of Western Australia and Cancer Council Tasmania. The Australasian Biospecimens Network-Oncology was funded by NHMRC (310670 & 628903). P. V. Loo is a postdoctoral researcher of the Research Foundation-Flanders (FWO).