Towards molecular characterization of sporadic epithelial ovarian carcinoma

All patients with advanced ovarian carcinoma are treated with a combination of
extensive debulking surgery and chemotherapy. Despite a good initial response
rate, most patients will develop progression of disease with a 5-year survival
of less than 30%. At present, we are not able to determine the optimal surgical
and/or chemotherapy regimen for an individual patient.
Comprehensive genomic studies of ovarian carcinoma have already identified
molecular abnormalities that affect outcome of the disease or could be targets
to guide therapy. However, although various pathways have been described that
play an important role in ovarian cancer, it is still not known which pathways
are most important for survival or how they could be influenced to improve the
response to treatment. It has been suggested that the different histological
subtypes of ovarian cancer have specific characteristics and this may have a
possible relation with different sensitivity to chemotherapeutic treatment.
However, reports are contradictory and no new treatment regimens have resulted
from this work so far.

The aim of the present study is to identify aberrations that play a significant
role in therapy response of ovarian cancer patients. RNA sequence/expression
and protein expression data will be combined and correlated to the extensive
clinical follow-up of our large patient cohort in order to elucidate the most
relevant pathways in carcinogenesis and response to therapy, and to uncover
whether post-transcriptional regulation plays a role in these processes.
Detailed knowledge of the transcriptome and proteome involved in carcinogenesis
and progression of ovarian carcinoma will help to classify subgroups that
differ in treatment response, like the ability to undergo optimal debulking
surgery, response to chemotherapy and survival. Based on the results clinical
trials for individualizing treatment of ovarian cancer patients will be set
up.

We plan to conduct a comprehensive study on our cohort of ovarian cancer
patients of whom all relevant information is known and who received treatment
according to standardized treatment protocols and of whom tumor tissue is
available. In addition to convantional techniques, we will use to relatively
new techniques to fully characterize ovarian carcinomas.
Using RNA sequencing (RNA-Seq) we will measure mRNA levels, study mutations,
and monitor the presence of non-coding RNAs in defined tumor tissues of various
histological subtypes.We aim to identify genes that differ between patients who
repond either very well or on the other hand poorly to treatment and who showed
recurrent disease quickly. Since the behaviour of the tumor will primarily be
determined by the proteins that the genes eventually code for, we subsequently
measure protein expression by a new and powerful mass spectrometry approach
called MSE. This approach is able to accurately identify and quantify hundreds
of proteins and is a leap forward in protein analysis technology.

The burden consists of a maximum of 5 minutes of the patient's time for the
withdrawal of extra blood.