Molecular profiling and personalized medicine within EURACAN in the SPECTA Arcagen study in comparison to the France Genomic Medicine 2025 Plan in the AURAGEN platform in peritoneal mesotheliomas

Our plain-English summary of Molecular profiling and personalized medicine within EURACAN in the SPECTA Arcagen study in comparison to the France Genomic Medicine 2025 Plan in the AURAGEN platform in peritoneal mesotheliomas, by S. Momenkhan, M. Morfouace, V. Kepenekian, et al (Translational Oncology, 2026).

The study

• Authors: S. Momenkhan, M. Morfouace, V. Kepenekian, O. Glehen, L. Villeneuve, J. Oliveira, S. Tejpar, S. Isaac, J. Fontaine, J.Y. Blay, J. Péron, N. Benzerdjeb
• Journal: Translational Oncology
• Published: 2026;69:102825
• Read it: PubMed · Publisher · Free full text

Abstract

Peritoneal mesothelioma (PM) is a rare aggressive cancer with limited therapeutic options upon progression. Two genomic profiling initiatives were launched to implement personalized medicine in rare cancers: the EURACAN molecular profiling and personalized medicine pathway and the France Genomic Medicine 2025 plan (AURAGEN). The aim of this study was to describe initial findings in PM and to compare these approaches in a real-world implementation setting. Herein, we present the results from a cohort of 56 patients with PM. Females represented 55.4% of patients; mean age was 55.9 years. The European (Arcagen) study profiled 26 patients and the AURAGEN platform profiled 42 patients. Genomic sequencing was performed using Foundation Medicine for the Arcagen cohort and whole-genome sequencing (WGS) for the AURAGEN cohort. Arcagen used FFPE tissue or blood depending on material availability, whereas AURAGEN relied on fresh frozen tumor tissue with paired blood (and RNA sequencing when feasible). Both cohorts displayed a predominance of alterations in BAP1, NF2, and CDKN2A/B. One patient with an ALK::STRN fusion was treated with Alectinib. AURAGEN identified a larger number of altered genes overall, while the proportion of therapeutic targets was similar between approaches. In conclusion, comprehensive molecular profiling offers potential therapeutic strategies for PM patients. Panel-based profiling and pan-genomic WGS appear complementary in real-world practice, each with distinct strengths and limitations.

Copyright © 2026 The Author(s). Published by Elsevier Inc. All rights reserved.

In plain English

This study described genomic testing of tumors from people with peritoneal mesothelioma (a cancer of the abdominal lining) under two programs. The European Arcagen study used a large Foundation Medicine gene panel on archived tumor tissue or blood. The French AURAGEN platform used whole-genome sequencing of fresh frozen tumor with paired blood. Patients were included retrospectively. Testing failed in 5 of 26 Arcagen and 7 of 42 AURAGEN patients, leaving 21 and 35 evaluable patients. Both groups most often showed alterations in BAP1, CDKN2A/B and NF2. AURAGEN reported alterations in 100 genes and Arcagen in 25, but the number of targetable alterations did not differ significantly. The median time from patient enrollment to delivery of the molecular report was 12 days for Arcagen and 50 days for AURAGEN. One Arcagen patient with an ALK::STRN fusion was switched to alectinib and was still on it 15 months later. The authors concluded that the two approaches found a similar proportion of treatment targets. They noted that sample types differed, that comparisons were exploratory, and that clinical outcomes were not analyzed statistically. The article does not discuss asbestos.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Retrospective descriptive comparison of two genomic profiling programs (a targeted gene panel versus whole-genome sequencing) in patients with peritoneal mesothelioma, with univariate statistical comparisons
• Who was studied: Patients with peritoneal mesothelioma. Arcagen enrolled 26 patients from five EURACAN centers in France, Belgium and Portugal between June 2019 and March 2022; 21 were evaluable. AURAGEN enrolled 42 patients with tissue collected at Hospices Civils de Lyon; 35 were evaluable. The 56 evaluable patients had a mean age of 55.9 years (range 24 to 80), and 31 of the 56 (55.4%) were female.
• Exposure: No asbestos or other occupational or environmental exposure is reported. The comparison was between profiling approaches. Arcagen used the Foundation Medicine panel on FFPE tumor tissue (n = 17) or blood (n = 4). AURAGEN used whole-genome sequencing of fresh frozen tumor tissue with blood, plus RNA sequencing when feasible.
• Main results:
  • At least one clinically relevant mutation was found in the majority of patients in both cohorts (more than 77%).
  • Most frequent alterations in the Arcagen cohort: BAP1 (n = 9, 42.8%), CDKN2A/B (n = 6, 28.6%), NF2 (n = 5, 23.8%) and SETD2 (n = 5, 23.8%).
  • Most frequent alterations in the AURAGEN cohort: BAP1 (n = 13, 37.1%), CDKN2A (n = 11, 31.4%), TP53 (n = 8, 22.8%) and NF2 (n = 9, 25.7%).
  • AURAGEN identified alterations in more genes than Arcagen (100 versus 25), but the number of targetable alterations did not differ significantly between the cohorts.
  • Tumor mutational burden was low in all patients except one in the Arcagen cohort. Microsatellite status was stable in all patients except one in the AURAGEN cohort.
  • The median turn-around time from patient enrollment to delivery of the molecular report was 12 days for Arcagen (range 8 to 48) and 50 days for AURAGEN (range 27 to 68). The authors state that this is an end-to-end workflow time, not sequencing time alone.
  • One Arcagen patient had an ALK::STRN fusion. That patient was switched to alectinib and was still on treatment 15 months later at data cutoff.
  • Four AURAGEN patients had gene fusions, but no targeted therapy was started based on them.
  • Across both cohorts, 44 patients had alterations considered targetable: 22 for clinical trials, 21 for off-label treatment and 1 for approved therapy.
• The authors' conclusion: The authors concluded that routine molecular profiling is of interest for patients with peritoneal mesothelioma, because clinically relevant alterations were found in most tumor samples. They added that the two approaches gave a similar proportion of therapeutic targets: whole-genome sequencing found more alterations but needs fresh biopsy, while the panel was faster.
• Limitations the authors state:
  • Three different sample types were used, which may limit comparisons and may bias cross-cohort differences.
  • Between-cohort comparisons were exploratory and were not adjusted for multiple testing.
  • Clinical outcomes (response and survival) were not analyzed statistically.
  • Only univariate comparisons were done, without multivariable adjustment, so differences may be influenced by confounders such as sex and disease extent.
  • Tumor mutational burden and microsatellite status could not be determined in about 25% of cases.
  • The limited sample size restricted the ability to detect smaller differences between groups.

Topics

Medical terms in this study, explained in our Lexicon: Molecular Profiling, Peritoneal Mesothelioma, BAP1, CDKN2A.

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