Systematic Assessment of the Applicability of Comprehensive
Genomic Testing Towards Better Cancer Clinical Diagnostics in
the Czech Republic

a 2025

Systematic Assessment of the Applicability of Comprehensive Genomic Testing Towards Better Cancer Clinical Diagnostics in the Czech Republic

PLEVOVÁ, Karla; Sabina PEŇÁZOVÁ; Patricie SKALÁKOVÁ; Jakub Paweł PORC; Hana SVOZILOVÁ et al.

Základní údaje

Originální název

Systematic Assessment of the Applicability of Comprehensive Genomic Testing Towards Better Cancer Clinical Diagnostics in the Czech Republic

Autoři

Vydání

Clinical Cancer Genomics Conference, Amsterodam, 2025

Další údaje

Jazyk

angličtina

Typ výsledku

Konferenční abstrakt

Obor

30204 Oncology

Stát vydavatele

Nizozemské království

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14740/25:00143673

Organizační jednotka

Středoevropský technologický institut

Klíčová slova anglicky

comprehensive genomic testing; whole-genome sequencing (WGS); chronic lymphocytic leukemia; clinical cancer diagnostics

Štítky

rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 10. 2. 2026 15:17, Mgr. Eva Dubská

Anotace

V originále

Recent technical advancements have allowed extensive implementation of sequencing technologies in clinical cancer research. However, their introduction in daily diagnostic use is hampered by multiple factors, such as the need for a systematic evaluation of their diagnostic yield over the routinely used, mostly low-throughput methods, financial aspects related to the healthcare reimbursement system, and setting standards of best laboratory practice for a wet-lab as well as dry-lab analytical part. We have decided to approach some of these aspects in the collaborative study Applicability of Comprehensive Genomic Testing 2wards Better Diagnostics (aka ACGT2) involving several centers across the Czech Republic. Here, we present the initial steps of our efforts. To evaluate the benefits of high-throughput methods, we implemented short-read whole-genome sequencing (WGS, Illumina), long-read WGS (Oxford Nanopore Technologies, ONT), and optical genome mapping (OGM, Bionano Genomics) to evaluate a consecutive cohort of cases with lymphoid malignancies as model diseases. We plan to test liquid biopsies as well as tissue specimens, depending on the specific diagnosis. For pilot experiments, we chose ten chronic lymphocytic leukemia cases with complex karyotypes and applied the three methods, aiming initially to investigate their genomic structural and copy number variants (SVs and CNVs, respectively). Short-read WGS was performed on tumor-normal paired DNA samples of every patient, whereas ONT and OGM on tumor samples only. Complementary data from routine diagnostic and experimental methods were available, including chromosomal banding analysis (CBA), multicolor FISH, chromosomal microarray (CMA), and chromatin conformation capture Micro-C. All these data types were used to evaluate chromosomal numerical and structural abnormalities detected in the samples against the hg38 genome reference. We implemented the Delly tool for SV and CNV calling from the sequencing methods. OGM data were analyzed and visualized using Bionano Access software. When comparing CNVs from short-read WGS, ONT, OGM, Micro-C, and CMA, we found that 65.5% of all changes were detected by at least three different methods. The remaining findings were mainly from genomic short-read WGS and CMA, which showed the highest accuracy and resolution, including the detection of minor clones. ONT proved very sensitive in SV analysis, detecting 65% of all breakpoints detected by at least one of the other methods. When comparing the results further with multicolor FISH and CBA, the short-read WGS, ONT, and OGM detected most findings in major clones (>20% mitoses) but repeatedly failed to detect specific rearrangements, such as dicentric chromosomes and derived chromosomes involving more than two chromosomes. For this purpose, the analysis against the T2T reference would be beneficial. Overall, we uncovered significantly greater SV complexity in all ten cases by combining short-read WGS, ONT, and OGM than identified by low-throughput methods. These pilot data will serve to adjust the analytical approaches for further larger patient cohorts.

Návaznosti

EH23_020/0008555, projekt VaV

Název: Využití komplexního genomického testování - na cestě k lepší diagnostice

Přiložené soubory

01_Abstract_book.pdf

Citovat

PLEVOVÁ, Karla; Sabina PEŇÁZOVÁ; Patricie SKALÁKOVÁ; Jakub Paweł PORC; Hana SVOZILOVÁ; Karolína ČERNOVSKÁ; Kamila STRÁNSKÁ; Eva ONDROUŠKOVÁ; Marie JAROŠOVÁ; Michael DOUBEK; Jana KOTAŠKOVÁ; Magdalena UVIROVA; Zuzana ZEMANOVA a Šárka POSPÍŠILOVÁ. Systematic Assessment of the Applicability of Comprehensive Genomic Testing Towards Better Cancer Clinical Diagnostics in the Czech Republic. In Clinical Cancer Genomics Conference, Amsterodam. 2025.

@proceedings{2553879,
   author = {Plevová, Karla and Peňázová, Sabina and Skaláková, Patricie and Porc, Jakub Paweł and Svozilová, Hana and Černovská, Karolína and Stránská, Kamila and Ondroušková, Eva and Jarošová, Marie and Doubek, Michael and Kotašková, Jana and Uvirova, Magdalena and Zemanova, Zuzana and Pospíšilová, Šárka},
   booktitle = {Clinical Cancer Genomics Conference, Amsterodam},
   keywords = {comprehensive genomic testing; whole-genome sequencing (WGS); chronic lymphocytic leukemia; clinical cancer diagnostics},
   language = {eng},
   title = {Systematic Assessment of the Applicability of Comprehensive Genomic Testing Towards Better Cancer Clinical Diagnostics in the Czech Republic},
   url = {https://www.ccg2025.eu/},
   year = {2025}
}

TY  - CONF
ID  - 2553879
AU  - Plevová, Karla - Peňázová, Sabina - Skaláková, Patricie - Porc, Jakub Paweł - Svozilová, Hana - Černovská, Karolína - Stránská, Kamila - Ondroušková, Eva - Jarošová, Marie - Doubek, Michael - Kotašková, Jana - Uvirova, Magdalena - Zemanova, Zuzana - Pospíšilová, Šárka
PY  - 2025
TI  - Systematic Assessment of the Applicability of Comprehensive Genomic Testing Towards Better Cancer Clinical Diagnostics in the Czech Republic
KW  - comprehensive genomic testing
KW  - whole-genome sequencing (WGS)
KW  - chronic lymphocytic leukemia
KW  - clinical cancer diagnostics
UR  - https://www.ccg2025.eu/
N2  - Recent technical advancements have allowed extensive implementation of sequencing technologies in clinical cancer research. However, their introduction in daily diagnostic use is hampered by multiple factors, such as the need for a systematic evaluation of their diagnostic yield over the routinely used, mostly low-throughput methods, financial aspects related to the healthcare reimbursement system, and setting standards of best laboratory practice for a wet-lab as well as dry-lab analytical part. We have decided to approach some of these aspects in the collaborative study Applicability of Comprehensive Genomic Testing 2wards Better Diagnostics (aka ACGT2) involving several centers across the Czech Republic. Here, we present the initial steps of our efforts. To evaluate the benefits of high-throughput methods, we implemented short-read whole-genome sequencing (WGS, Illumina), long-read WGS (Oxford Nanopore Technologies, ONT), and optical genome mapping (OGM, Bionano Genomics) to evaluate a consecutive cohort of cases with lymphoid malignancies as model diseases. We plan to test liquid biopsies as well as tissue specimens, depending on the specific diagnosis. For pilot experiments, we chose ten chronic lymphocytic leukemia cases with complex karyotypes and applied the three methods, aiming initially to investigate their genomic structural and copy number variants (SVs and CNVs, respectively). Short-read WGS was performed on tumor-normal paired DNA samples of every patient, whereas ONT and OGM on tumor samples only. Complementary data from routine diagnostic and experimental methods were available, including chromosomal banding analysis (CBA), multicolor FISH, chromosomal microarray (CMA), and chromatin conformation capture Micro-C. All these data types were used to evaluate chromosomal numerical and structural abnormalities detected in the samples against the hg38 genome reference. We implemented the Delly tool for SV and CNV calling from the sequencing methods. OGM data were analyzed and visualized using Bionano Access software. When comparing CNVs from short-read WGS, ONT, OGM, Micro-C, and CMA, we found that 65.5% of all changes were detected by at least three different methods. The remaining findings were mainly from genomic short-read WGS and CMA, which showed the highest accuracy and resolution, including the detection of minor clones. ONT proved very sensitive in SV analysis, detecting 65% of all breakpoints detected by at least one of the other methods. When comparing the results further with multicolor FISH and CBA, the short-read WGS, ONT, and OGM detected most findings in major clones (>20% mitoses) but repeatedly failed to detect specific rearrangements, such as dicentric chromosomes and derived chromosomes involving more than two chromosomes. For this purpose, the analysis against the T2T reference would be beneficial. Overall, we uncovered significantly greater SV complexity in all ten cases by combining short-read WGS, ONT, and OGM than identified by low-throughput methods. These pilot data will serve to adjust the analytical approaches for further larger patient cohorts.
ER  -

PLEVOVÁ, Karla; Sabina PEŇÁZOVÁ; Patricie SKALÁKOVÁ; Jakub Paweł PORC; Hana SVOZILOVÁ; Karolína ČERNOVSKÁ; Kamila STRÁNSKÁ; Eva ONDROUŠKOVÁ; Marie JAROŠOVÁ; Michael DOUBEK; Jana KOTAŠKOVÁ; Magdalena UVIROVA; Zuzana ZEMANOVA a Šárka POSPÍŠILOVÁ. Systematic Assessment of the Applicability of Comprehensive Genomic Testing Towards Better Cancer Clinical Diagnostics in the Czech Republic. In \textit{Clinical Cancer Genomics Conference, Amsterodam}. 2025.

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