TY - JOUR
T1 - Genomic profiling of tissue and blood predicts survival outcomes in patients with resected pleural mesothelioma
AU - de Miguel-Perez, Diego
AU - Pickering, Edward M.
AU - Malapelle, Umberto
AU - Grier, William
AU - Pepe, Francesco
AU - Pisapia, Pasquale
AU - Russo, Gianluca
AU - Pinto, Joseph A.
AU - Russo, Alessandro
AU - Troncone, Giancarlo
AU - Culligan, Melissa J.
AU - Scilla, Katherine A.
AU - Mehra, Ranee
AU - Mohindra, Pranshu
AU - Arrieta, Oscar
AU - Cardona, Andres F.
AU - Del Re, Marzia
AU - Sachdeva, Ashutosh
AU - Hirsch, Fred R.
AU - Wolf, Andrea
AU - Friedberg, Joseph S.
AU - Rolfo, Christian
N1 - Publisher Copyright:
© 2023
PY - 2024/1
Y1 - 2024/1
N2 - Purpose: Pleural mesothelioma (PM) is an aggressive tumor still considered incurable, in part due to the lack of predictive biomarkers. Little is known about the clinical implications of molecular alterations in resectable PM tissues and blood. Here, we characterized genetic alterations to identify prognostic and predictive biomarkers in patients with resected PM. Experimental Design: Targeted next-generation sequencing was performed in retrospective pleural tumor tissue and paired plasma samples from stage IB-IIIB resected PM. Association between prognosis and presence of specific mutations was validated in silico. Results: Thirty PM tissues and paired blood samples from 12 patients were analyzed. High tissue tumor mutational burden (TMB) (>10 mutations/Mb), tissue median minor allele frequency (MAF) (>9 mutations/Mb), and blood TMB (>6 mutations/Mb), tissue KMT2C, PBRM1, PKHD1,EPHB1 and blood LIFR mutations correlated with longer disease-free survival and/or overall survival. High concordance (>80%) between tissue and blood was found for some mutations. Conclusions: Tissue TMB and MAF, blood TMB, and specific mutations correlated with outcomes in patients with resected PM and should be further studied to validate their role as prognostic biomarkers and potentially predictive factors for combinations with immune-checkpoint inhibitors. This suggest that molecular profiling could identify longer survivors in patients with resected PM.
AB - Purpose: Pleural mesothelioma (PM) is an aggressive tumor still considered incurable, in part due to the lack of predictive biomarkers. Little is known about the clinical implications of molecular alterations in resectable PM tissues and blood. Here, we characterized genetic alterations to identify prognostic and predictive biomarkers in patients with resected PM. Experimental Design: Targeted next-generation sequencing was performed in retrospective pleural tumor tissue and paired plasma samples from stage IB-IIIB resected PM. Association between prognosis and presence of specific mutations was validated in silico. Results: Thirty PM tissues and paired blood samples from 12 patients were analyzed. High tissue tumor mutational burden (TMB) (>10 mutations/Mb), tissue median minor allele frequency (MAF) (>9 mutations/Mb), and blood TMB (>6 mutations/Mb), tissue KMT2C, PBRM1, PKHD1,EPHB1 and blood LIFR mutations correlated with longer disease-free survival and/or overall survival. High concordance (>80%) between tissue and blood was found for some mutations. Conclusions: Tissue TMB and MAF, blood TMB, and specific mutations correlated with outcomes in patients with resected PM and should be further studied to validate their role as prognostic biomarkers and potentially predictive factors for combinations with immune-checkpoint inhibitors. This suggest that molecular profiling could identify longer survivors in patients with resected PM.
KW - Blood mutations
KW - Prognostic biomarkers
KW - Resected pleural mesothelioma
KW - Tissue mutations
UR - http://www.scopus.com/inward/record.url?scp=85177737416&partnerID=8YFLogxK
U2 - 10.1016/j.ejca.2023.113457
DO - 10.1016/j.ejca.2023.113457
M3 - Article
AN - SCOPUS:85177737416
SN - 0959-8049
VL - 196
JO - European Journal of Cancer
JF - European Journal of Cancer
M1 - 113457
ER -