Comparative analysis of genetic variants in pleural fluids and solid tissue biopsies of pleural mesothelioma patients: Implications for molecular heterogeneity assessment

Our plain-English summary of Comparative analysis of genetic variants in pleural fluids and solid tissue biopsies of pleural mesothelioma patients: Implications for molecular heterogeneity assessment, by R. Silvestri, F. Rea, M. Vitiello, et al (Heliyon, 2024).

The study

• Authors: R. Silvestri, F. Rea, M. Vitiello, G. Moretti, V. Aprile, M. Lucchi, P. Aretini, C.M. Mazzanti, S. Landi, F. Gemignani
• Journal: Heliyon
• Published: 2024;10(11):e32152
• Cited by: 2 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Objectives: This study aims to determine whether the sequencing of DNA extracted from pleural fluids (PFs) of Pleural Mesothelioma (PM) patients accurately represents the genetic information obtained from the solid tissue counterpart biopsies with particular attention to the identification of single nucleotide variants (SNVs).

Materials And Methods: Single pleural biopsy, PFs, and blood were collected from PM patients. DNA was extracted from these samples and then subjected to Whole-Exome Sequencing.

Results: A higher number of SNVs was identified in PFs than in solid tissue biopsies (STBs). Most SNVs were detected in PFs samples but not in STBs samples, while only a few SNVs were detected in STBs samples but not in PFs samples.

Conclusion: The current findings support the notion that PFs might offer a more robust depiction of cancer's molecular diversity. Nonetheless, the current outcomes challenge the assertion that liquid biopsies can encompass the entirety of intra-patient variations. Indeed, a subset of potential cancer-driver SNVs was exclusively identified in STBs. However, relying solely on STBs would have precluded the detection of significant SNVs that were exclusively present in PFs. This implies that while PFs serve as a valuable complement to STBs, they do not supplant them.

© 2024 The Authors. Published by Elsevier Ltd.

In plain English

This study from Pisa, Italy, asked whether DNA from the fluid around the lungs (pleural fluid) of people with pleural mesothelioma carries the same genetic information as a tumour tissue sample (biopsy). Three patients, two 79-year-old men and one 77-year-old woman, all with the epithelioid type, gave blood, pleural fluid and a biopsy during diagnostic thoracoscopy between December 2020 and February 2021. The authors sequenced the protein-coding DNA of each sample and compared single-letter DNA changes (variants). Few variants were shared by the biopsy and the fluid's liquid and cell parts: 65, 29 and 8 in the three patients, or 6, 3 and 0.6 percent of each patient's biopsy variants. In genes often mutated in mesothelioma, most variants (6 of 7 in one patient, 8 of 10 in each of the others) appeared in fluid samples but not the biopsy. SETD2 changes appeared only in biopsies. The authors concluded that pleural fluid could complement, but not replace, biopsies. They noted the limitation that only a tiny part of one of several biopsy specimens per patient was analysed. The study did not examine asbestos exposure.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory genetic comparison (whole-exome sequencing) of matched tumour biopsy, pleural fluid and blood samples from three patients
• Who was studied: Three patients with pleural mesothelioma, all of the epithelioid subtype: two 79-year-old males (C001, C008) and one 77-year-old female (C002). They were recruited at the University Hospital of Cisanello (Pisa) between December 2020 and February 2021 and underwent diagnostic thoracoscopy.
• Exposure: Not studied. The article compares sources of tumour DNA and does not report the patients' asbestos exposure. The introduction only notes that pleural mesothelioma is associated with past asbestos exposure.
• Main results:
  • Variants shared by the biopsy, the pleural fluid supernatant and the cell pellet numbered 65 in patient C001 (6 % of the biopsy's total), 29 in C002 (3 %) and 8 in C008 (0.6 %).
  • In genes frequently mutated in mesothelioma, most variants were found in pleural fluid samples but not in the biopsy: 6 of 7 in patient C001, and 8 of 10 in each of patients C002 and C008.
  • Variants in BAP1, FAT4, LATS2, MUC16 and PTCH1 were not detected in biopsy samples. NF2 variants were detected only in cell pellet samples.
  • SETD2 was the only one of these genes found mutated in biopsy samples (patients C002 and C008) but not in fluid samples.
  • The fluid supernatant sample of patient C008 produced little sequencing data because little pleural fluid was recovered.
• The authors' conclusion: The authors concluded that pleural fluid samples could be more representative of the mutational landscape than tissue biopsies. Because some variants were found only in biopsies, they concluded that fluid samples are a complement to tissue biopsies, not a replacement.
• Limitations the authors state:
  • Few biopsy specimens were used. For each patient, only a tiny fraction of one of the several tissue biopsy specimens taken for diagnosis was analysed. For ethical reasons no extra biopsies could be taken, so the biopsy results may not reflect the tumour's full variability.
  • The variants identified do not necessarily represent clinically relevant variants.
  • Loss of one copy of BAP1 may have been present but could not be detected with the methods used.

Topics

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Pleural Biopsy.

Related studies

• The genetic susceptibility in the development of malignant pleural mesothelioma: somatic and germline variants, clinicopathological features and implication in practical medical/surgical care: a narrative review — M.T. Congedo, E.C. West, et al. (2024)
• Liquid Biopsies from Pleural Effusions and Plasma from Patients with Malignant Pleural Mesothelioma: A Feasibility Study — G. Moretti, P. Aretini, et al. (2021)
• Updates on the cytogenetics and molecular genetics of bone and soft tissue tumors. Mesothelioma — A.A. Sandberg, J.A. Bridge (2001)
• Digital PCR for Detecting Loss of BAP1 and MTAP in Pleural Fluids of Mesothelioma Patients: Perspectives in the Diagnosis — G. Rosini, G. Alì, et al. (2026)
• Genetic alterations of malignant pleural mesothelioma: association with tumor heterogeneity and overall survival — L. Quetel, C. Meiller, et al. (2020)
• Malignant Pleural Mesothelioma: Genetic and Microenviromental Heterogeneity as an Unexpected Reading Frame and Therapeutic Challenge — D.M. Abbott, C. Bortolotto, et al. (2020)

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