Comparative Analysis of Comprehensive Genomic Profile in Thymomas and Recurrent Thymomas Reveals Potentially Actionable Mutations for Target Therapies

Lococo, Filippo; De Paolis, Elisa; Evangelista, Jessica; Dell’Amore, Andrea; Giannarelli, Diana; Chiappetta, Marco; Campanella, Annalisa; Sassorossi, Carolina; Cancellieri, Alessandra; Calabrese, Fiorella; Conca, Alessandra; Vita, Emanuele; Minucci, Angelo; Bria, Emilio; Castello, Angelo; Urbani, Andrea; Rea, Federico; Margaritora, Stefano; Scambia, Giovanni

doi:10.3390/ijms25179560

Open AccessArticle

Comparative Analysis of Comprehensive Genomic Profile in Thymomas and Recurrent Thymomas Reveals Potentially Actionable Mutations for Target Therapies

by

Filippo Lococo

^1,2,*,†

,

Elisa De Paolis

^3,4,†,

Jessica Evangelista

^1,2,

Andrea Dell’Amore

⁵,

Diana Giannarelli

⁶

,

Marco Chiappetta

²

,

Annalisa Campanella

²,

Carolina Sassorossi

²,

Alessandra Cancellieri

⁷,

Fiorella Calabrese

⁸,

Alessandra Conca

⁸,

Emanuele Vita

⁹,

Angelo Minucci

⁸

,

Emilio Bria

^9,10,

Angelo Castello

¹¹,

Andrea Urbani

³,

Federico Rea

⁵,

Stefano Margaritora

^1,2,‡ and

Giovanni Scambia

^12,‡

¹

Thoracic Surgery, Università Cattolica del Sacro Cuore, 00168 Rome, Italy

²

Thoracic Surgery, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy

³

Clinical Chemistry, Biochemistry and Molecular Biology Operations (UOC), Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy

⁴

Departmental Unit of Molecular and Genomic Diagnostics, Genomics Core Facility, Gemelli Science and Technology Park (G-STeP), Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy

⁵

Thoracic Surgery Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, 35122 Padova, Italy

⁶

Epidemiology and Biostatistics Facility, Gemelli Science and Technology Park (G-STeP), Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy

⁷

Unit of Pathology, Fondazione Policlinico Gemelli IRCCS, 00168 Rome, Italy

⁸

Pathology Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, 35122 Padova, Italy

⁹

UOSD Oncologia Toraco-Polmonare, Comprehensive Cancer Center, Fondazione Policlinico Universitario Ago-stino Gemelli IRCCS, 00168 Rome, Italy

¹⁰

UOC Oncologia Medica, Ospedale Isola Tiberina—Gemelli Isola, 00186 Roma, Italy

¹¹

Nuclear Medicine Department, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy

¹²

Division of Gynecologic Oncology, Fondazione Policlinico Universitario A. Gemelli-IRCCS, 00168 Rome, Italy

Show full affiliation list

Hide full affiliation list

^*

Author to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

^‡

These authors contributed equally to this work.

Int. J. Mol. Sci. 2024, 25(17), 9560; https://doi.org/10.3390/ijms25179560

Submission received: 15 July 2024 / Revised: 31 August 2024 / Accepted: 2 September 2024 / Published: 3 September 2024

(This article belongs to the Special Issue Advances in Molecular Biology and Treatment of Thymic Epithelial Tumors)

Download

Browse Figures

Review Reports Versions Notes

Abstract

Molecular profiles of thymomas and recurrent thymomas are far from being defined. Herein, we report an analysis of a comprehensive genetic profile (CGP) in a highly selected cohort of recurrent thymomas. Among a cohort of 426 thymomas, the tissue was available in 23 recurrent tumors for matching the biomolecular results obtained from primary and relapse samples. A control group composed of non-recurrent thymoma patients was selected through a propensity score match analysis. CGP was performed using the NGS Tru-SightOncology assay to evaluate TMB, MSI, and molecular alterations in 523 genes. CGP does not differ when comparing initial tumor with tumor relapse. A significantly higher frequency of cell cycle control genes alterations (100.0% vs. 57.1%, p = 0.022) is detected in patients with early recurrence (<32 months) compared to late recurrent cases. The CGPs were similar in recurrent thymomas and non-recurrent thymomas. Finally, based on NGS results, an off-label treatment or clinical trial could be potentially proposed in >50% of cases (oncogenic Tier-IIC variants). In conclusion, CGPs do not substantially differ between initial tumor vs. tumor recurrence and recurrent thymomas vs. non-recurrent thymomas. Cell cycle control gene alterations are associated with an early recurrence after thymectomy. Multiple target therapies are potentially available by performing a comprehensive CGP, suggesting that a precision medicine approach on these patients could be further explored.

Keywords: NGS; recurrent thymoma; surgery; CGP; gene profile; clinical trials

Share and Cite

MDPI and ACS Style

Lococo, F.; De Paolis, E.; Evangelista, J.; Dell’Amore, A.; Giannarelli, D.; Chiappetta, M.; Campanella, A.; Sassorossi, C.; Cancellieri, A.; Calabrese, F.; et al. Comparative Analysis of Comprehensive Genomic Profile in Thymomas and Recurrent Thymomas Reveals Potentially Actionable Mutations for Target Therapies. Int. J. Mol. Sci. 2024, 25, 9560. https://doi.org/10.3390/ijms25179560

AMA Style

Lococo F, De Paolis E, Evangelista J, Dell’Amore A, Giannarelli D, Chiappetta M, Campanella A, Sassorossi C, Cancellieri A, Calabrese F, et al. Comparative Analysis of Comprehensive Genomic Profile in Thymomas and Recurrent Thymomas Reveals Potentially Actionable Mutations for Target Therapies. International Journal of Molecular Sciences. 2024; 25(17):9560. https://doi.org/10.3390/ijms25179560

Chicago/Turabian Style

Lococo, Filippo, Elisa De Paolis, Jessica Evangelista, Andrea Dell’Amore, Diana Giannarelli, Marco Chiappetta, Annalisa Campanella, Carolina Sassorossi, Alessandra Cancellieri, Fiorella Calabrese, and et al. 2024. "Comparative Analysis of Comprehensive Genomic Profile in Thymomas and Recurrent Thymomas Reveals Potentially Actionable Mutations for Target Therapies" International Journal of Molecular Sciences 25, no. 17: 9560. https://doi.org/10.3390/ijms25179560

APA Style

Lococo, F., De Paolis, E., Evangelista, J., Dell’Amore, A., Giannarelli, D., Chiappetta, M., Campanella, A., Sassorossi, C., Cancellieri, A., Calabrese, F., Conca, A., Vita, E., Minucci, A., Bria, E., Castello, A., Urbani, A., Rea, F., Margaritora, S., & Scambia, G. (2024). Comparative Analysis of Comprehensive Genomic Profile in Thymomas and Recurrent Thymomas Reveals Potentially Actionable Mutations for Target Therapies. International Journal of Molecular Sciences, 25(17), 9560. https://doi.org/10.3390/ijms25179560

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Menu

Comparative Analysis of Comprehensive Genomic Profile in Thymomas and Recurrent Thymomas Reveals Potentially Actionable Mutations for Target Therapies

Abstract

Share and Cite

Article Metrics

Article Access Statistics

Further Information

Guidelines

MDPI Initiatives

Follow MDPI