Malignant cells from pleural fluids in malignant mesothelioma patients reveal novel mutations

Abstract

Short term cultures of tumour cells from MM pleural effusions offer an accessible alternative to surgical tumour biopsies in the study of MM genomics and reveal novel mutations of interest. Pleural effusion tumour cells provide an opportunity for the monitoring of tumour dynamics, treatment response and the clonal evolution of MM tumours.

Well-Differentiated Papillary Mesothelioma of the Peritoneum is Genetically Distinct from Malignant Mesothelioma

“…11 What is surprising in our results is the absence of the TRAF7 and CDC42 alterations reported by Yu et al 7 and Stevers et al 11 in WDPM and by the same group in adenomatoid tumors 31 . Alterations in TRAF7 has also been reported in malignant mesotheliomas 4,20,32…”

Identification of a CD8+ T-cell response to a predicted neoantigen in malignant mesothelioma

“…Comprehensive patient demographics have been detailed previously. 18 Somatic mutation burden was not associated with a survival benefit. 18 Predicted neoantigens identified in all patient samples…”

“…Over 90% of MM patients develop pleural effusion during the course of their disease, which can be a rich source of cells shed from the primary tumor 17 and we have previously shown that the tumor cells found in the malignant pleural effusions of MM patients carry many of the hallmark mutations found in solid MM tumors, as well as a wealth of novel individual mutations. 18 In our murine MM model, we have previously demonstrated a strong spontaneous endogenous CD8+ T cell response to a predicted MM tumor neoantigen. 19 A recent sequencing study of 98 primary human MM tumor samples found that 59% of all identified somatic mutations resulted in predicted MHC class I-binding neoantigens.…”

“…Potential neoantigens were studied in 27 MM patient pleural effusions. 18 The median age of the group at diagnosis was 65 years (range 45-88 years). Median survival was 15 months (range 1-61 months) ( Table 1).…”

“…21 A total of 2236 patient HLA specific neoantigens were predicted across all of the MM tumor cell samples from 48% (607/1256) of the previously identified protein coding somatic mutations ( Figure 1). 18 A median of 68 (range 7-258) predicted neoantigens were detected across the samples (Figure 1). Of these, a median of 32 (range 15-93) predicted neoantigens were observed to bind (IC50 ≤ 500 nM) to MHC class I in the mutated but not the wild-type state ( Figure 1).…”