Abstract 1734P
Background
Malignant pleural and peritoneal mesothelioma are rare malignancies with unacceptable poor prognosis and limited treatment options. The genomic landscape of these diseases is mainly characterized by loss of tumor suppressor genes and mutations in DNA repair genes. Currently, data from next-generation sequencing (NGS) of mesothelioma tumors is restricted to a limited number of cases; moreover, data comparing molecular features of mesothelioma from pleural and peritoneal origin with NGS are lacking.
Methods
We analysed 1113 pleural mesothelioma and 355 peritoneal mesothelioma samples from patients sequenced through December 2020. All tumors were sequenced by NGS with the FoundationOne® or FoundationOne®CDx (Foundation Medicine) test for detection of substitutions, insertion-deletions, copy-number alterations and selected rearrangements in at least 324 cancer genes. Microsatellite instability was called on at least 95 loci and tumor mutational burden (TMB) was calculated on 0.8-1.2 Mb.
Results
This analysis revealed alterations in 65 genes with a prevalence higher than 2% of all patients. Alterations in BAP1, CDKN2A, CDKN2B, NF2, MTAP, TP53, and SETD2 occurred with a prevalence of at least 10%. Peritoneal, compared to pleural mesothelioma, was characterized by a lower prevalence of alterations in CDKN2A, CDKN2B and MTAP. Alterations in Hedgehog pathway-related genes (PTCH1/2 and SUFU) and Hippo pathway-related gene (NF2) as well as KRAS, EGFR, PDGFRA/B, ERBB2 and FGFR3 were detected in both cohorts. Table: 1734P
| Peritoneal (n=355) | Pleural (n=1113) | p_val (fdr) | |
| BAP1 | 47.9% | 45.0% | NS |
| CDKN2A | 25.9% | 48.2% | <0.01 |
| CDKN2B | 19.4% | 42.1% | <0.01 |
| MTAP | 15.4% | 32.3% | <0.01 |
| NF2 | 26.5% | 32.8% | <0.05 |
| PBRM1 | 15.8% | 6.8% | <0.01 |
| SETD2 | 10.4% | 10.3% | NS |
| TP53 | 14.9% | 17.8% | NS |
| Hedgehog pathway | 1.1% | 2.0% | NS |
| Hippo pathway | 29.0% | 36.1% | <0.05 |
Conclusions
Precision medicine has significantly improved the outcome of patients with cancer; molecular alterations, even if rare, may enable targeted treatment options. Here, we have analysed the largest cohort of patients with mesothelioma so far, for molecular aberrations by NGS. In a proportion of patients, alterations targetable with drugs available or under development were detected. These results suggest possible value for molecular profiling in mesothelioma.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
Z. Fleischmann: Financial Interests, Personal, Full or part-time Employment: Foundation Medicine; Financial Interests, Personal, Stocks/Shares: Roche. E. Sokol: Financial Interests, Personal, Full or part-time Employment: FoundationMedicine; Financial Interests, Personal, Stocks/Shares: Roche. A. Curioni-Fontecedro: Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Bristol Meyer Squibb; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Takeda. All other authors have declared no conflicts of interest.