Přehled o publikaci
2025
Incidental Germline Findings During Comprehensive Genomic Profiling of Pancreatic and Colorectal Cancer: Single-center, Molecular Tumor Board Experience
EID, Michal; Jakub TRIZULJAK; Renata TASLEROVÁ; Martin GRYC; Jakub VLAŽNÝ et al.Basic information
Original name
Incidental Germline Findings During Comprehensive Genomic Profiling of Pancreatic and Colorectal Cancer: Single-center, Molecular Tumor Board Experience
Authors
EID, Michal; Jakub TRIZULJAK; Renata TASLEROVÁ; Martin GRYC; Jakub VLAŽNÝ; Sára VILMANOVÁ; Martina JELÍNKOVÁ; Alena HOMOLOVÁ; Štěpán TUČEK; Jan HLAVSA; Tomáš GROLICH; Zdeněk KALA; Zdeněk KRÁL and Ondřej SLABÝ
Edition
Mutagenesis, OXFORD, OXFORD UNIV PRESS, 2025, 0267-8357
Other information
Language
English
Type of outcome
Article in a journal
Country of publisher
United Kingdom of Great Britain and Northern Ireland
Confidentiality degree
is not subject to a state or trade secret
References:
Marked to be transferred to RIV
No
Organization
Lékařská fakulta – Repository – Repository
UT WoS
EID Scopus
Keywords in English
next-generation sequencing; pancreatic cancer; colorectal cancer; germline variants; somatic variants
Links
LX22NPO5102, research and development project. MUNI/A/1558/2023, interní kód Repo. NU23-08-00241, research and development project. NCMG II, large research infrastructures.
Changed: 15/3/2026 00:50, RNDr. Daniel Jakubík
Abstract
In the original language
Multidisciplinary molecular tumor boards (MTB) are already well established in many comprehensive cancer centers and play an important role in the individual treatment planning for cancer patients. Comprehensive genomic profiling of tumor tissue based on next-generation sequencing is currently performed for diagnostic and mainly predictive testing. If somatic genomic variants are identified, which are suspected to be pathogenic germline variants (PGVs), MTB propose genetic counseling and germline DNA testing. Commonly used comprehensive genomic profiling approaches of tumor tissue do not include a matched germline DNA control. Therefore, the detection of PGVs could be only predicted based on the content of tumor cells (CTC) in selected tumor area (%) and variant allele frequency score (%). For conclusion, the role of a medical geneticist is essential in these cases. The overall prevalence of PGVs in patients with pancreatic ductal adenocarcinoma (PDAC) and colorectal cancer (CRC) is approximately 10%. In this single-center study, we present 37 patients with PDAC and 48 patients with CRC who were presented at MTB and tested using the large combined DNA/RNA sequencing panel. Content of tumor cells and variant allele frequency scores were evaluated in all tested patients. In case of suspicion of PGV and no previous genetic testing based on the standard guidelines, genetic counseling was recommended regardless of age, sex, and family history. In the PDAC subgroup, five patients were recommended by MTB for genetic counseling based on suspicious genetic findings. Based on a medical geneticist's decision, germline DNA sequencing was performed in four of these cases, and all of them tested positive for PGV in the following genes: ATM, ATM, BRCA1, and BRCA2. In the CRC subgroup, no PGV was confirmed in the two patients genetically tested based on the MTB recommendations. Furthermore, we present data from our center's registry of patients with PDAC and CRC who underwent genetic counseling and germline DNA testing based on the standard screening criteria. Our data confirm that comprehensive genomic profiling of tumor tissue can identify patients with hereditary forms of PDAC, who could remain unidentified by standard screening for hereditary forms of cancer.
