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February 28-March 01, 2019 | Paris, France
Palliative Care, Obstetrics and Gynecology
Stroke and Clinical Trials
International Conference on
Joint Event on
International Conference on
&
Journal of Research and Reports in Gynecology and Obstetrics | Volume: 3
19q12 amplified and non-amplified subsets of high grade serous ovarian cancer with overexpression of
cyclin E1 differ in their molecular drivers and clinical outcomes
Paul Waring
University of Melbourne, Australia
Objectives:
Readily apparent cyclin E1 expression occurs
in 50% of HGSOC, but only half are linked to 19q12 locus
amplification. The amplified/cyclin E1hi subset has
intact BRCA1/2, unfavourable outcome and is potentially
therapeutically targetable. We studied whether non-
amplified/cyclin E1hi HGSOC has similar characteristics.
We also assessed the expression of cyclin E1 degradation-
associated proteins, FBXW7and USP28, as potential drivers
of high cyclin E1 expression in both subsets.
Methods:
262HGSOCcaseswereanalysedbyinsituhybridization
for 19q12 locus amplification and immunohistochemistry for
cyclin E1, URI1 (another protein encoded by the 19q12 locus),
FBXW7 and USP28 expression. Tumours were classified by
19q12 amplification status and correlated to cyclin E1 and
URI1 expression, (CHECK FOR SPACING), BRCA1/2 germline
mutation, FBXW7 and USP28 expression, and clinical outcomes.
Additionally, we assessed the relative genomic instability
of amplified/cyclin E1hi and non-amplified/cyclin E1hi
groups of HGSOC datasets from The Cancer Genome Atlas.
Results:
Of the 82 cyclin E1hi cases, 43 (52%) were amplified
and 39 (48%) were non-amplified. Unlike amplified tumours,
non-amplified/cyclin E1hi tumour status was not mutually
exclusive with gBRCA1/2 mutation. The non-amplified/cyclin
E1hi group had significantly increased USP28, while the
amplified/cyclin E1hi cancers had significantly lower FBXW7
expression consistent with a role for both in stabilizing cyclin E1.
Notably, only the amplified/cyclin E1hi subset was associated
with genomic instability and had a worse outcome than
nonamplified/cyclin E1hi group.
Conclusions:
Amplified/cyclin E1hi and non-amplified/cyclin
E1hi tumours have different pathological and biological
characteristics and clinical outcomes indicating that they are
separate subsets of cyclin E1hi HGSOC.
e:
pwaring@unimelb.edu.auRes Rep Gynaecol Obstet, Volume 3
DOI: 10.4066/2591-7366-C1-003