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Molecular signature in malignant pleural mesothelioma (MPM): Preliminary data of Italian RAMES Study

Date

21 Oct 2018

Session

Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology

Presenters

Francesca Zanelli

Citation

Annals of Oncology (2018) 29 (suppl_8): viii670-viii682. 10.1093/annonc/mdy304

Authors

F. Zanelli1, M. Pagano1, C. Bonelli1, R. Gnoni1, L. Boni2, G.L. Ceresoli3, M. Larocca1, M. Tiseo4, P. Zucali5, F. Grosso6, F. Cappuzzo7, A. CIARROCCHI8, F. TORRICELLI8, C. Pinto1

Author affiliations

  • 1 Oncology Unit, AUSL di Reggio Emilia-IRCCS, 42100 - Reggio Emilia/IT
  • 2 Istituto Toscano Tumori, clinical trial coordinating center, AOU careggi ,, firenze/IT
  • 3 Oncology, Humanitas Gavazzeni, 24125 - Bergamo/IT
  • 4 Medical Oncology, AOU di Parma, 43126 - Parma/IT
  • 5 Oncology, Humanitas Clinical and Research Hospital, Rozzano/IT
  • 6 Oncology/hematology, Ospedale di Alessandria, 15121 - Alessandria/IT
  • 7 Dipartimento Di Oncologia Medica, Azienda Unità Sanitaria Locale della Romagna, 48100 - Ravenna/IT
  • 8 Laboratory Research, AUSL-IRCCS Reggio Emilia, 42100 - Reggio Emilia/IT
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Background

MPM is a highly aggressive pleural tumor associated with asbestos exposure. The ability to analyze entire genomes opens the door to identification of new treatments.

Methods

RAMES is a ongoing phase II study to evaluate the efficacy and the safety of the addition of ramucirumab to gemcitabine as the second-line treatment in 160 pts with MPM. We designed a custom panel covering 1040 amplicons spanning 33 genes frequently altered in MPM. To establish the genetic asset of MPMs we used an amplicon-based next generation sequencing approach.

Results

To date, 40 FFPE mesothelioma cancer tissues were successfully sequenced A total of 2930 variants passing quality filters were detected. Focusing on potentially functional alterations, polymorphisms and non-coding variants were excluded, leaving 143 alterations in 23 of the analyzed genes. Of these, 59.4% (85/143) were missense mutations, 22.4% (32/143) lead to frameshift alteration of the gene sequence, 13.3% (19/143) were splice variants, while the remaining 4.9% (7/143) were start loss, stop gain alterations and deletion. 97.5% of patients (39/40) displayed at least one mutation, while the average number of mutations per sample was 3.6 (range 0-8), confirming the high mutational load of these tumors. The most frequently altered genes identified were PIK3CA (62.5%), RDX (40%), MXRA5 (20%), BAP1 (15%), NF2 (15%). Molecular analyses have been correlated with Histology and Stage (thoracic vs extrathoracic MPM). We found the following NF2, PIK3CA, RDX altered genes in 9 biphasic tumor and MXRA5, NF2, PIK3CA, RDX, CUL1, BAP1, NF2, TAOK1 altered genes in 31 ephitelioid tumor. We observed a significant correlation between mutations in RDX gene (23.1%) and extrathoracic MPM. CUL1 and RDX genes were found in pts with progression free survival ≥6 months from prior treatment.

Conclusions

This preliminary data supports the generation of a genetic signature based on tumor mutational status useful to discriminate MPM with different clinico-pathological features and possible correlation with treatment choice.

Clinical trial identification

Legal entity responsible for the study

AUSL-IRCCS Reggio Emilia.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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