ECP 2023 Abstracts

S134 Virchows Archiv (2023) 483 (Suppl 1):S1–S391 13 *Navarra’s Universitary Hospital, Spain Background & objectives: Next generation sequencing (NGS) have identified recurrent mutations in cholangiocarcinomas (CCAs) in tissue samples and recently in bile cell-free DNA Objective: To test NGS in bile cell free DNA as a tool in the diagnosis of malignant biliary stenosis Methods: Prospective 68 patient study between January 2017 and December 2020 at Navarra University Hospital(Spain) with clinical malignant bile duct stenosis. Sixty nine bile duct(BD) cytologies and 12 BD biopsies were patho- logicaly evaluated.) 68 bile samples were collected. NGS panel (Oncomine Pan- Cancer) was performed in bile samples and compared with the pathological diagnosis.Mean follow up was 15. 5 months. Results: The pathological diagnosis was: n = 32 malignant (24 CCAs and nine pancreatic ductal adenocarcinomas PDACs) , n=26 benign, n=9 indeterminate. Bile mutations (BM) were identified in all CCAs (sensitivity 100%) and in seven PDACs. Mutations identified were KRAS, TP53, ERBB3, GNAS, FBXW7, ERB2, IDH2, MAPK2K1 and FGFR3. After follow up 14 of the 23 patient diagnosed as benign, developed a malignant stenosis. BM were identified in 18/23 of these patients. In indeterminate diagnosis (n=9) BM were identified in eight patients, in the follow up all of these developed a malignant tumour Conclusion: Pathological diagnosis of malignancy in biliary stric- tures are very specific (100%). Bile mutations are the same found in tissue samples of CCAs (KRAS, TP53, ERBB3, GNAS, FBXW7, ERB2, IDH2, MAPK2K1 and FGFR3). In clinical suspected malignant strictures, diagnosed as benign or inde- terminate, assessment for bile mutations could determine the clinical follow up and is a strong indicator for repeating cytology or biopsy in order to avoid a false negative diagnosis. PS-24-010 BC-miR: monitoring breast cancer-related miRNA profile in blood sera - a prosperous approach for tumour detection T. Pankotai*, B. Borsos, Z. Páhi, Z. Ujfaludi, F. Sükösd, S. Bankó, G. Pankotai-Bodó, O. Olah-Nemeth *Hungarian Centre of Excellence, University of Szeged, Albert Szent- Györgyi Medical School, Institute of Pathology, Hungary Background & objectives: Breast cancer is the most frequent cancer with a high fatality rate amongst women worldwide. Diagnosing at an early stage is challenging, and due to the limitations of the currently used techniques, including mammography and imaging diagnostics, it remains unascertained. Methods: We monitored the expressional changes of 15 pre-selected miRNAs in a large cohort, including 65 patients with breast cancer and 42 healthy individuals. We performed thorough statistical analyses on the cohort sample set and determined the diagnostic accuracy of individual and multiple miRNAs. Results: Serum biomarkers can be a solution for this as they can be isolated in a less painful, more cost-effective, and minimally invasive manner. In this study, we shed light on the relevant role of multi- ple microRNAs (miRNAs) as potential biomarkers in breast cancer diagnosis. We generated a miRNA cluster, including various num- bers of correlated miRNAs and monitored which ones seemed to be the most suitable for discriminating the healthy individuals from BC patients. These analyses underlined the promiscuous relevance of miR- 15a+miR-16 and miR-15a+miR-16+miR-221 clusters in recognizing breast cancer with high prevalence and specificity. Conclusion: In our cohort, the miR-15a+miR-16+miR-221 combina- tion turned out to be the most promising multiple miRNAs, which may be suitable for further diagnostic purposes related to breast can- cer. According to our data, we believe that if future validation stud- ies supported our data, clinical implementation of miR-15a+miR- 16+miR-221 would be of great importance in ameliorating the progression and recurrence of breast cancer. This research was funded by the National Research, Development and Innovation Office grant NKFI295 FK 132080. T.P. was funded by the János Bolyai Research Scholarship of the Hungarian Academy of Sci- ences BO/27/20 and UNKP-22-5-SZTE-318, UNKP-22-3-SZTE-274. The project has received funding from the EU’s Horizon 2020 research and innovation program under grant agreement No.739593. Project no. TKP-2021-EGA-05 has been implemented with the support pro- vided by the Ministry of Culture and Innovation of Hungary from the National Research, Development and Innovation Fund, financed under the TKP2021-EGA funding scheme. PS-24-011 Novel kinase-activating fusions in lung adenocarcinomas G. Raskin*, E. Preobrazhenskaya, F. Zagrebin, R. Mulkidzhan, E. Saitova, I. Bizin, E. Imyanitov *Dr. Berezin Medical Insitute, Russia Background & objectives: Gene fusions involving protein kinases are druggable therapeutic targets, which are characteristic for a subset of lung adenocarcinomas. They are particularly common in young-onset cases, females and non-smokers. Methods: RNA-based NGS analysis for 650 kinase genes was per- formed for 87 lung adenocarcinomas obtained from 77 young-onset patients (age range: 33-50 years; median age: 44 years; 53 males and 24 females) and 10 non-smoking females over 50 years old (age range: 58-79 years; median age: 68 years). All these tumours were negative for alterations involving EGFR/BRAF/MET/ALK/ROS1/RET/NTRK1-3/ HER2/KRAS/NRAS genes. Results: Kinome RNAseq revealed 84 chimeric transcripts; most of them were frameshifts, with only 26 fusion variants being in-frame. There were 20 interchromosomal and 64 intrachromosomal rearrange- ments. Kinase domain was completely or partially lost in 6 and 12 out of 26 tumours with in-frame translocations, respectively. Eight rearrange- ments preserved the entire kinase domain within a chimeric transcript: MAPK10::RASGEF1B 4q21.22-23del3.95Mb, STK38::CDC73 t(4;1) (p21.31;q31.2), BCR::PKHD1 t(22;6)(q11.23;p12.3), CLTC::RPS6KB1 17q23.1del0.2Mb, CDC42BPG::ATG2A 11q13.1del0.05Mb, ATXN2L : : SMG1 16p11 . 2 - 12 . 3de l 9 . 9Mb , WASF: :FGR 1p36.11del0.12Mb and ZNHIT3::PRKCA 17q12-24.3del29.8Mb. These gene fusions were analysed in 1059 NSCLCs, which were negative for all known actionable mutations, however no additional instances of these translocations was observed. Conclusion: This study identified eight novel potentially actionable kinase gene fusions. The spectrum of recurrent kinase-activating tranlocations does not extend beyond ALK/ROS1/RET/NTRK1-3 gene fusions, with other presumably druggable rearrangements being excep- tionally rare and diverse. Funding: Russian Science Foundation, grant 17-75-30027 PS-24-012 Clinical validation of NTRK gene fusion companion diagnostics (CDx) claims for TruSightTMOncology Comprehensive (EU) assay V. Sementchenko*, M. Harris, D. Vavrek, A. Martinez, C. Chen, K. Shen, L. Yun, T. Pawlowski *Illumina, Inc., USA