Sub-type Specific Genomic Mutations in sBOTs

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ClinicalTrials.gov Identifier: NCT03883542

Recruitment Status : Recruiting

First Posted : March 21, 2019

Last Update Posted : May 16, 2023

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Sponsor:

Information provided by (Responsible Party):

Stefan Cosyns, Universitair Ziekenhuis Brussel

Study Description

Brief Summary:

The aim of this study is to identify different origin in carcinogenesis between serous borderline ovarian tumors presenting a. without implants, b. with non-invasive implants, c. with invasive implants and d. with micropapillary pattern.

The presence of specific mutations could suggest for a more aggressive primary treatment if a higher risk of recurrence can be expected.

Condition or disease	Intervention/treatment
Ovarian Neoplasm Epithelial	Genetic: genomic mutations study

Detailed Description:

Introduction Borderline Ovarian Tumors (BOTs) behave indolently in the vast majority of cases and the prognosis is usually favorable. There is more evidence that two subtypes of BOTs represent a higher risk of recurrence or even progression to an invasive ovarian cancer. In case of a presentation with a micro-papillary grow pattern or when invasive implants are diagnosed the prognosis tend to be less favorable.

Genome sequencing in ovarian cancer helped to differentiate two different pathways in the carcinogenesis.

Low grade serous carcinomas evolving from adenofibromas or borderline tumors over non-invasive micropapillary serous borderline tumors to invasive micropapillary serous carcinoma, show frequent mutations in the Kirsten Rat Sarcoma gene (KRAS), B-Raf Kinase gene(BRAF), Erb-B2 Receptor Tyrosine Kinase 2 gene (ERBB2), Phosphatase and Tensin homolog gene (PTEN), Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha gene (PIK3CA) and Catenin Beta 1 gene (CTNNB1). This pathway is called Type I and is characterized by a slow step-wise process. These low-grade invasive tumors are indolent and are known with a better outcome than high-grade invasive tumors.

In contrast the Type II pathway development of invasive tumors is rapid and vast majority of tumors show a Tumor Protein p53 (TP53) mutation and loss of Breast Cancer type 1 susceptibility protein (BRCA1).

The presence of specific mutations could suggest for a more aggressive primary treatment if a higher risk of recurrence can be expected.

Study Design

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Study Type :	Observational
Estimated Enrollment :	20 participants
Observational Model:	Case-Only
Time Perspective:	Retrospective
Official Title:	Sub-type Specific Genomic Mutations in Serous Borderline Ovarian Tumors
Actual Study Start Date :	January 2017
Estimated Primary Completion Date :	December 31, 2023
Estimated Study Completion Date :	April 30, 2024

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Ovarian cancer

MedlinePlus related topics: Ovarian Cancer

Genetic and Rare Diseases Information Center resources: Ovarian Cancer

U.S. FDA Resources

Groups and Cohorts

Group/Cohort	Intervention/treatment
serous BOT simple serous BOT ovarian tissue	Genetic: genomic mutations study Sequencing of the DNA samples extracted from the subgroups serous BOT tissue, serous BOT tissue with non-invasive implants and serous BOT tissue with micropapillary grow pattern will undergo a panel testing for Type 1 genes (small panel 15-40 mutations) AND p53 AND BRCA testing Sequencing of the DNA samples extracted from the serous BOT tissue with invasive implants will undergo a more comprehensive examination (large panel +- 1000 genes checked)
serous BOT with non-invasive implants BOT ovarian tissue presenting with non-invasive implants	Genetic: genomic mutations study Sequencing of the DNA samples extracted from the subgroups serous BOT tissue, serous BOT tissue with non-invasive implants and serous BOT tissue with micropapillary grow pattern will undergo a panel testing for Type 1 genes (small panel 15-40 mutations) AND p53 AND BRCA testing Sequencing of the DNA samples extracted from the serous BOT tissue with invasive implants will undergo a more comprehensive examination (large panel +- 1000 genes checked)
sBOT with micropapillary grow pattern BOT ovarian tissue presenting with micropapillary grow pattern	Genetic: genomic mutations study Sequencing of the DNA samples extracted from the subgroups serous BOT tissue, serous BOT tissue with non-invasive implants and serous BOT tissue with micropapillary grow pattern will undergo a panel testing for Type 1 genes (small panel 15-40 mutations) AND p53 AND BRCA testing Sequencing of the DNA samples extracted from the serous BOT tissue with invasive implants will undergo a more comprehensive examination (large panel +- 1000 genes checked)
serous BOT with invasive implants sBOT ovarian tissue presenting with invasive implants at the time of diagnosis	Genetic: genomic mutations study Sequencing of the DNA samples extracted from the subgroups serous BOT tissue, serous BOT tissue with non-invasive implants and serous BOT tissue with micropapillary grow pattern will undergo a panel testing for Type 1 genes (small panel 15-40 mutations) AND p53 AND BRCA testing Sequencing of the DNA samples extracted from the serous BOT tissue with invasive implants will undergo a more comprehensive examination (large panel +- 1000 genes checked)

Outcome Measures

Primary Outcome Measures :

genetic mutations [ Time Frame: 2020 ]
amount and type of genetic mutations in different subgroups will be analyzed and compared between the different subgroups. Are the mutations suggestive for a type I or type II pathway differentiation?

Biospecimen Retention: Samples With DNA

Macrodissection of borderline ovarian tumor tissue. DNA extraction from paraffin embedded material for genetic analysis.

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	Female
Accepts Healthy Volunteers:	No
Sampling Method:	Probability Sample

Study Population

Patients with proven serous bordeline ovarian tumors.

Criteria

Inclusion Criteria:

Paraffin embedded material from the original borderline ovarian tumor must be present and of good quality for DNA extraction.
Original slides are available for central pathological review.

Exclusion Criteria:

Presence of invasive ovarian carcinoma.

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03883542

Contacts

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Contact: Stefan Cosyns, Dr	24776020 ext +32	scosyns@uzbrussel.be

Locations

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Belgium
Universitair Ziekenhuis UZBrussel	Recruiting
Jette, Brussels, Belgium, 1090
Contact: Stefan Cosyns, Md 24776020 ext 0032 Scosyns@uzbrussel.be

Sponsors and Collaborators

Universitair Ziekenhuis Brussel

Investigators

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Principal Investigator:	stef cosyns, dr	UZBrussel

More Information

Publications:

Morice P, Uzan C, Fauvet R, Gouy S, Duvillard P, Darai E. Borderline ovarian tumour: pathological diagnostic dilemma and risk factors for invasive or lethal recurrence. Lancet Oncol. 2012 Mar;13(3):e103-15. doi: 10.1016/S1470-2045(11)70288-1.

Vang R, Shih IeM, Kurman RJ. Ovarian low-grade and high-grade serous carcinoma: pathogenesis, clinicopathologic and molecular biologic features, and diagnostic problems. Adv Anat Pathol. 2009 Sep;16(5):267-82. doi: 10.1097/PAP.0b013e3181b4fffa.

Despierre E, Lambrechts D, Neven P, Amant F, Lambrechts S, Vergote I. The molecular genetic basis of ovarian cancer and its roadmap towards a better treatment. Gynecol Oncol. 2010 May;117(2):358-65. doi: 10.1016/j.ygyno.2010.02.012. Epub 2010 Mar 7.

Kurman RJ, Shih IeM. The origin and pathogenesis of epithelial ovarian cancer: a proposed unifying theory. Am J Surg Pathol. 2010 Mar;34(3):433-43. doi: 10.1097/PAS.0b013e3181cf3d79.

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Responsible Party:	Stefan Cosyns, Principal Investigator, Universitair Ziekenhuis Brussel
ClinicalTrials.gov Identifier:	NCT03883542
Other Study ID Numbers:	sBOT
First Posted:	March 21, 2019 Key Record Dates
Last Update Posted:	May 16, 2023
Last Verified:	May 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No

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Studies a U.S. FDA-regulated Drug Product:	No
Studies a U.S. FDA-regulated Device Product:	No

Keywords provided by Stefan Cosyns, Universitair Ziekenhuis Brussel:


low malignant potential serous

Additional relevant MeSH terms:

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Ovarian Neoplasms Endocrine Gland Neoplasms Neoplasms by Site Neoplasms Ovarian Diseases Adnexal Diseases Genital Diseases, Female Female Urogenital Diseases	Female Urogenital Diseases and Pregnancy Complications Urogenital Diseases Genital Neoplasms, Female Urogenital Neoplasms Genital Diseases Endocrine System Diseases Gonadal Disorders

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