PhD Scientific Days 2023
Budapest, 22-23 June 2023
Pathology - Posters C
Investigation of the presumed RICTOR amplification and its potential role in targeted therapy of different malignant tumours
Előadó neve
Sztankovics, Dániel
Neptun code
ZO54P8
Előadó munkahelye
Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary
Előadó telefonszáma
+36702579264
Előadó e-mail címe
sztankovics.daniel@gmail.com
Az előadás címe
Investigation of the presumed RICTOR amplification and its potential role in targeted therapy of different malignant tumours
Szerző(k) neve és munkahelye
Dániel Sztankovics1, Ildikó Krencz1, Gábor Bedics1, Gergő Papp1, Dorottya Moldvai1, Titanilla Dankó1, Noémi Nagy1, Ákos Nagy1, András Rókusz1, Judit Pápay1, Csaba Bödör1, Anna Sebestyén1
1 Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary
Bemutatás módja
Poszter
Szekció
Pathology - Posters C
Language of the presentation
Hungarian
Preferred session
Pathology and Oncology
Összefoglaló szövege
Introduction. Failures in the signalling network, including mTOR (mechanistic target of rapamycin) hyperactivity, contribute to tumorigenesis. Increased activity and overexpression of the elements of the mTOR complexes (mTORC1 and C2) have been described in many cancers, especially in association with poor prognosis. Regarding mTORC2 complex hyperactivity, the overexpression of Rictor (rapamycin-insensitive companion of mTOR), the scaffolding protein of the mTORC2 complex, could contribute to tumour cell survival, uncontrolled growth and tumour progression (migration). Additionally, Rictor amplification has been described in certain tumour types with targetable mTOR/mTORC2 signalling.
Aims. We aimed to analyse RICTOR copy number variations (CNVs) detected by routine diagnostic next-generation sequencing (NGS) as signs of potential RICTOR amplification in more than 400 samples from various malignant tumours.
Method. "Gold-standard" fluorescence in situ hybridisation (FISH) and Droplet Digital PCR (ddPCR) were used to study the predicted RICTOR amplification from NGS CNV results. Furthermore, the detected RICTOR amplification status was compared with Rictor and p-Akt (Ser473) protein expression using immunohistochemistry.
Results. High CNVs of RICTOR were detected in 37 cases (8.8%) of the 420 malignant tumour samples based on data obtained by routine diagnostic NGS. Analysing these cases, FISH and ddPCR validated 16 and 11 among the 37 cases (43.2% and 29.7%, respectively). Additionally, increased Rictor protein expressions and mTORC2 complex activity were also detected in 12 or 14 (37.8% or 32.4%) and 7 (18.9%) cases using two different Rictor and p-Akt (Ser473) antibody immunostainings, respectively.
Conclusion. Based on our results, higher copy numbers (CNV higher than 3) detected by NGS could highlight RICTOR amplification and initiate further validation by FISH or ddPCR in certain previously described tumour types. Additionally, Rictor and p-Akt (Ser473) protein expression analyses in correlation with Rictor overexpression or mTORC2 complex hyperactivation could initiate specific mTOR-targeted therapies.
Funding. Our research was supported by TKP2021-EGA-24 and NKFI-FK-128404, NKFI-K-142799 (National Research, Development and Innovation Office), EFOP-3.6.3-VEKOP-16-2017-00009 (D.S., D.M. and T.D.).
University and Doctoral School
Semmelweis University, Doctoral School of Pathological Sciences
Supervisor
Anna Sebestyén
Publication of my abstract
I do not give consent to the publication of my abstract on the website of the congress.
Kind
Szabad
Status
elfogadva
Accepted presentation method
poszter
Előadás fájl jóváhagyás
nem rendelkezett róla
Előadó
6049
Start
11:00
End
11:05
Authors (legacy)
Dániel Sztankovics1, Ildikó Krencz1, Gábor Bedics1, Gergő Papp1, Dorottya Moldvai1, Titanilla Dankó1, Noémi Nagy1, Ákos Nagy1, András Rókusz1, Judit Pápay1, Csaba Bödör1, Anna Sebestyén1
1 Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary