The role of mucin cell-free DNA detection as a new marker for the study of acellular pseudomyxoma peritonei of appendicular origin by liquid biopsy
EntityUAM. Departamento de Cirugía; Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD)
10.1177/1758835920928233Therapeutic Advances in Medical Oncology 12 (2020): 1-12
ISSN1758-8340 (print); 1758-8359 (online)
Funded byThe authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was funded by a grant from the ‘FIS-ISCIII-FEDER’ [Fondo de Investigaciones Sanitarias-Instituto de Salud Carlos III-Fondo Europeo de Desarrollo Regional (European Regional Development Fund)], Ministry of Health, Spain (grant number PI17/01233).
ProjectGobierno de España. PI17/01233
Subjectsacellular pseudomyxoma peritonei; droplet digital PCR; KRAS; liquid biopsy; mucin; Medicina
Rights© 2020 The Authors
Esta obra está bajo una licencia de Creative Commons Reconocimiento-NoComercial 4.0 Internacional.
Background: Acellular pseudomyxoma peritonei (aPMP) is a rare peritoneal malignancy characterized by the accumulation of large amounts of mucin (lacking tumor cells) in the peritoneum. Many cases account for several kilograms of mucin to be screened by the pathologist. This is a comprehensive study of three patients with aPMP, whose tumors showed KRAS mutation, allowing for the tracking of this marker by liquid biopsy. Methods: Pre and post-surgery plasma, and mucin removed during cytoreductive surgery were collected from the patients. KRAS mutations were analyzed using droplet digital polymerase chain reaction (ddPCR). Mucin was injected in mice. KRAS and cytokine levels were measured in plasma of the mice using ddPCR and a magnetic bead-based assay. Mucin microbiome was analyzed by 16S rRNA sequencing. Results: KRAS mutations were detected in mucin cell-free DNA (cfDNA) from the three patients but not in the pre or post-surgery plasma. Electron microscopy detected microparticles (diameter <0.4 µm) in mucin. Mucin from one patient grew up inside the peritoneal cavity of mice and human KRAS was identified in mucin cfDNA, but not in plasma. All mucins showed the same bacterial profile. Cytokine levels were slightly altered in mice. Conclusions: The three aPMP patients included in this study shared some common aspects: the absence of tumor cells in mucin, the presence of KRAS mutated cfDNA in mucin, and the absence of this tumor-derived mutation in the bloodstream, providing additional information to the routine pathological examinations and suggesting that mucin cfDNA could potentially play a role in aPMP recurrence and prognosis.
Google Scholar:García Olmo, Damián - Olmedillas-López, Susana - Cortés-Guiral, Delia - Villarejo, Pedro - López Rojo, Irene - Guadalajara Labajo, Héctor - García Gómez-Heras, Soledad - García Arranz, Mariano Andrés
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