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Optimized precision oncology through implementation of a comprehensive molecular analysis pipeline - relevance for

Nuwar Harb1, Marcel Romey1, Albert Grass1

  • 1Institute of Pathology, Philipps-University Marburg and University Hospital Marburg (UKGM), Marburg, Germany.

Cancer Genetics
|April 8, 2026
PubMed
Abstract

Insights

Larger next-generation sequencing (NGS) gene panels provide more clinically relevant therapy options for molecular tumor boards (MTB). Sufficient genomic coverage is essential for accurate tumor mutational burden (TMB) calculation in cancer care.

Area of Science:

  • Oncology
  • Genomics
  • Personalized Medicine

Background:

  • Personalized medicine relies on identifying molecular targets for tailored therapies.
  • The efficacy of different next-generation sequencing (NGS) panel sizes in identifying these targets is under investigation.

Purpose of the Study:

  • To compare the clinical utility of larger NGS gene panels (> 1 Mb) versus smaller panels for identifying actionable molecular targets.
  • To assess the impact of panel size on molecular tumor board (MTB) recommendations and therapy selection.

Main Methods:

  • Analysis of 281 patients' tumors using a 430-gene DNA panel (1.3 Mb) and a RNA-fusion panel.
  • Comparison of results with a smaller 185-gene DNA panel (618 kb).

Main Results:

  • Molecular alterations were detected in 97.2% of tumors.
  • 170 patients (60.5%) received molecular-stratified therapy recommendations.
  • The larger 430-gene panel identified actionable variants in five additional genes, crucial for 8.8% of recommendations. High tumor mutational burden (TMB) alone guided 4.1% of recommendations.

Conclusions:

  • Sufficient genomic coverage via larger DNA panels is critical for reliable TMB calculation.
  • Establishing minimum genomic coverage standards is essential for comprehensive cancer care.
Keywords:
Molecular tumor boardNext-generation sequencingPanel sequencingPersonalized medicineTumor molecular profilingTumor mutational burden

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