Optimized precision oncology through implementation of a comprehensive molecular analysis pipeline – relevance for additional therapeutic options
BACKGROUND AND PURPOSE: Personalized medicine is guided by an expanding array of molecular targets. This study investigates whether larger next-generation sequencing (NGS) gene panels (> 1 Mb) yield more clinically relevant therapy options in molecular tumor boards (MTB) compared to smaller panels. PATIENTS AND METHODS: We analyzed 281 consecutive patients using a 430-gene DNA panel (1.3 Mb) combined with a RNA-fusion panel and compared the findings to a 185-gene DNA panel (618 kb). RESULTS: Molecular alterations were detected in 97.2 % of tumors with either oncogenic variants and/or gene fusions. Among these, 170 (60.5 %) received a molecular-stratified therapy recommendation from the local MTB. Only 8.8 % depended on the expanded 430-gene DNA panel, and additionally identified actionable variants in five additional genes. High TMB alone enabled 4.1 % of MTB recommendations. CONCLUSION: Our findings indicate that sufficient genomic coverage in DNA panels is essential for reliable TMB calculation, defining a minimal standard for genomic cancer care.
Authors
- Gernot G. U. Rohde (ORCID: https://orcid.org/0000-0002-5193-7755)
- Marvin Görg
- Akira Hattesohl (ORCID: https://orcid.org/0000-0002-1307-3773)
- Niklas Gremke (ORCID: https://orcid.org/0000-0002-9015-3646)
- Fiona R. Rodepeter
- Anja Rinke (ORCID: https://orcid.org/0000-0002-8156-2915)
- Moritz Jesinghaus (ORCID: https://orcid.org/0000-0002-0018-5661)
- Elisabeth Maurer (ORCID: https://orcid.org/0000-0003-3431-6233)
- Charis Faoro
- Elisabeth Mack (ORCID: https://orcid.org/0000-0003-4061-494X)
- Cornelia Brendel (ORCID: https://orcid.org/0000-0003-1612-9557)
- Christian Wilhelm (ORCID: https://orcid.org/0000-0002-5574-925X)
- Ursula Keber (ORCID: https://orcid.org/0000-0002-0539-7065)
- Christer Groeben (ORCID: https://orcid.org/0000-0002-1769-0402)
- Jonas Schäfer (ORCID: https://orcid.org/0000-0001-8852-1457)
- Marcel Romey (ORCID: https://orcid.org/0000-0002-3668-2934)
- Andreas Burchert (ORCID: https://orcid.org/0000-0002-8411-8844)
- Sebastian Adeberg (ORCID: https://orcid.org/0000-0001-8463-514X)
- Thomas Wündisch
- Uwe Wagner (ORCID: https://orcid.org/0000-0002-5866-6273)
- Thomas M. Gress (ORCID: https://orcid.org/0000-0002-9333-5461)
- Nadine Frickel
- Christopher Nimsky (ORCID: https://orcid.org/0000-0002-8216-9410)
- Jorge Ramon Riera
- Jörg Hoffmann (ORCID: https://orcid.org/0000-0003-3488-4804)
- Boris A. Stuck
- Nuwar Harb
- Julia Teply-Szymanski
- Anne-Sophie Litmeyer
- Detlef K. Bartsch
- Florentin von Kügelgen
- Steffen Ruchholtz
- Martin Gschnell
- Andreas Neubauer
- Sonja Gehring
- Lukas Frey
- Albert Grass
- Carsten Denkert
Institutions
- Philipps University of Marburg (DE)
- Universitätsklinikum Gießen und Marburg (DE)
- Wilhelm Stahl Provincial Hospital (ZA)
Publication Details
- Journal
- Cancer Genetics
- Published
- 2026-04-03
- DOI
- https://doi.org/10.1016/j.cancergen.2026.04.001
- Primary Topic
- Cancer Genomics and Diagnostics
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Bundesministerium für Bildung und Forschung
- José Carreras Leukämie-Stiftung