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Molecular markers of pituitary tumor development, progression and therapy response

 

 

Project Title: „Molecular markers of pituitary tumor development, progression and therapy response” 

Funding:  European Regional Development Fund (ERDF), Measure 1.1.1.1 “Industry-Driven Research”

Project Nr.: 1.1.1.1/16/A/066

Period: 1st January 2017 – 31 st December 2019

Project costs: 648 600,28 EUR

Principle Investigator: Dr. biol., Assoc. Prof. J. Kloviņš 

 

 Pituitary adenomas are rare benign tumors that are responsible for serious health complications with increased morbidity and mortality. Despite the extensive studies the primary genetic defects determining the tumorigenesis of pituitary adenomas is still unclear and very heterogeneous. Another problem is the inaccessibility of the pituitary gland that hampers the use of molecular biomarkers for observation or differential treatment purpose. Accordingly, to successfully treat pituitary adenomas more rigorous diagnostic approaches are needed that would allow for detailed tumor subtype classification to enable personalized treatments. The project is aimed to help in solving these issues. The main objective of this project is to investigate molecular determinants of pituitary adenoma development and progression and to identify the crucial factors linked to variability in clinical outcome that could further be applied as biomarkers for improvement of pituitary tumor treatment therapies. Specifically we aim (1) to identify disease specific somatic genetic variations in different types of pituitary adenoma and use this information to characterize the separate cell populations in adenoma resections as well as markers for non-invasive monitoring of adenomas, (2) to identify vesicle associated based RNA markers that differentiate between healthy subjects and pituitary adenoma patients, as well as different clinical outcomes and treatment efficiency, (3) to estimate the best combination of variable biomarkers that can predict PA growth dynamics and recurrence probability. Presented project will perform original and innovative experiments including the genetic characterization of the tumor specific cell populations, estimation of tumor specific cell free DNA and identification of vesicle associated RNA as liquid biopsy based biomarkers that has not been done in case of pituitary adenoma studies.

Information published: 02.01.2017.


Progress of the project

1 January 2017 - 31 March 2017

During this period intensive preparation for project implementation has been carried out, criteria have been selected for patient identification from Genome Database of Latvian Population collection, the characterization have been started of the patients to be included in the research. These actions have facilitated collection establishment of samples and associated data for project implementation.  Additionally, the collection of supplementary clinical data has begun, as well as recruitment of new patients. The experimental approaches have been developed for massive parallel sequencing and cell free DNA studies, the experimental protocols and methodology have been developed. Also procedures for cell sorting have been created.

Information published: 31.03.2017.


Progress of the project

1 April 2017 - 31 June 2017

Project specific database of pituitary adenoma patients has been developed based on Genome Database of Latvian population, including clinical information about the patients, this database will be updated during the course of the project. Four exoms of pituitary adenoma have been sequenced and primary analysis undertaken to compare presence of somatic mutations in primary and regrown tumors. Following the developed protocol cells from two pituitary adenoma biopsies have been sorted and isolation of tumor specific RNA have started. Isolation method for cell free DNA from patients’ plasma have been optimized and cell free DNA isolated from five patients’ plasma. The protocol development for exosome and miRNA isolation from plasma has been started.

Information published: 30.06.2017.

 

Progress of the project

1 July 2017 - 30 September 2017

The designed project specific database cross-checked and arranged according to project’s needs, additional clinical data and new pituitary adenoma samples have been collected. DNA exome sequencing have been continued, including library preparation, quality control and sequencing. Results have been anaysed comparing patients genomic, primary and recurrent tumor somatic DNA. Genomic rearrangements have been studied and discrimination in different types of mutations (insertions, deletions, translocations etc.). Cell sorting experiments have been further conducted, as well as RNA extraction from pituitary adenoma tumor cell types.  Cell free circulating DNA isolation have been performed for six samples and first exosome and miRNA isolation experiments executed.

Information published: 29.09.2017.



Mājas lapas izstrādi finansēja ERAF 2.1.1.2. aktivitātes projekts Nr. 2010/0196/2DP/2.1.1.2.0/10/APIA/VIAA/004 "Latvijas biomedicīnas pētījumu integrācija Eiropas zinātnes telpā".