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Updated: Jan 10, 2026
Detecting Somatic Genetic Alterations in Tumor Specimens by Exon Capture and Massively Parallel Sequencing
Published on: October 18, 2013
Clinical benefit of additional whole-exome sequencing over panel sequencing in an all-comer real-world molecular
E Krieghoff-Henning1, T Michaeli2, T Boch3
1Department of Personalized Oncology, University Hospital Mannheim, Heidelberg University, Mannheim, Germany; Division of Personalized Medical Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany; DKFZ Hector Cancer Institute at the University Medical Center Mannheim, Mannheim, Germany; Division of Translational Medical Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany; National Center for Tumor Diseases (NCT), NCT Heidelberg, a partnership between DKFZ and Heidelberg University Hospital, Heidelberg, Germany.
Background:
Panel sequencing, whole-exome sequencing (WES) and whole-genome sequencing (WGS) often uncover therapeutic targets for cancer patients. However, it is still largely unclear to what extent patients directly benefit from broader analyses over panel sequencing alone.
Materials And Methods:
We analyzed the molecular findings and recommendations issued by our molecular tumor board (MTB) in a cohort of patients who had received both a well-established diagnostic panel of medium size (up to 203 genes) and in-house WES, focusing on the number of recommendations that were issued on the basis of WES results only.
Results:
Our cohort consisted of 38 patients with advanced cancers, of whom about two-thirds had common and one-third had rare cancers. They received a total of 45 (range 0-4) treatment recommendations overall, of which 29 had a clinical level of evidence (LoE) and/or entailed a feasible study enrollment and were thus considered highly actionable. Sixteen recommendations, of which seven were highly actionable, were issued only on the basis of WES results (five own, two previous WES). Three out of those seven recommendations and one additional recommendation based on a previous large panel were related to complex molecular biomarkers such as homologous recombination deficiency or high tumor mutational burden, with poly (ADP-ribose) polymerase inhibitors or checkpoint inhibitors as recommended treatment. As expected, a higher proportion of the WES-only recommendations (63% versus 42% of recommendations overall) were based on non-clinical LoEs. One of eight recommendations implemented so far was based on biomarkers derived by WES only.
Conclusions:
In our MTB, WES enabled some additional clinically highly actionable recommendations for selected patients, suggesting that some patients do benefit from additional WES. These recommendations were often related to complex biomarkers, which may in principle also be derived from larger panels. These findings should be re-investigated prospectively in larger cohorts.
Insights
Whole-exome sequencing (WES) provided additional actionable treatment recommendations for advanced cancer patients, particularly for complex biomarkers. Further prospective studies are needed to confirm the benefits of WES over panel sequencing alone.
Area of Science:
- Oncology
- Genomics
- Personalized Medicine
Background:
- Genomic sequencing, including panel sequencing, whole-exome sequencing (WES), and whole-genome sequencing (WGS), identifies potential therapeutic targets in cancer.
- The clinical utility of broader genomic analyses beyond standard panel sequencing remains incompletely understood.
Purpose of the Study:
- To evaluate the added value of whole-exome sequencing (WES) in a molecular tumor board (MTB) setting.
- To determine the number of actionable treatment recommendations derived solely from WES results compared to panel sequencing.
Main Methods:
- Analysis of molecular findings and recommendations from a molecular tumor board (MTB).
- Inclusion of patients who underwent both medium-sized gene panel sequencing and in-house whole-exome sequencing (WES).
- Focus on recommendations issued exclusively based on WES data.
Main Results:
- Out of 45 total recommendations for 38 advanced cancer patients, 16 were WES-only, with 7 being highly actionable.
- WES-only recommendations frequently involved complex biomarkers like homologous recombination deficiency or high tumor mutational burden.
- One implemented recommendation was based solely on WES-derived biomarkers.
Conclusions:
- Whole-exome sequencing (WES) offers additional clinically actionable recommendations for select cancer patients, especially those with complex biomarkers.
- The benefits of WES may extend beyond what larger gene panels can provide.
- Prospective validation in larger patient cohorts is recommended.
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