Cell-Free DNA from Ascites and Pleural Effusions: Molecular Insights into Genomic Aberrations and Disease Biology

• Published in: Molecular cancer therapeutics Vol. 16; no. 5; pp. 948 - 955
• Main Authors: Husain, Hatim, Nykin, David, Bui, Nam, Quan, Daniel, Gomez, German, Woodward, Brian, Venkatapathy, Sumathi, Duttagupta, Radha, Fung, Eric, Lippman, Scott M., Kurzrock, Razelle
• Format: Journal Article
• Language: English
• Published: United States American Association for Cancer Research Inc 01.05.2017
• Subjects: Aberration; Adult; Aged; Aged, 80 and over; Amplification; Ascites; Ascites - blood; Ascites - genetics; Ascitic fluid; Biology; Biopsy; Blood; Breast cancer; Cancer; Cell Line, Tumor; Cell-Free Nucleic Acids - blood; Cell-Free Nucleic Acids - genetics; Chromosome rearrangements; Class I Phosphatidylinositol 3-Kinases - genetics; Copy number; Cyclin-dependent kinase 4; Cyclin-Dependent Kinase 4 - genetics; Cytology; Deoxyribonucleic acid; DNA; DNA Copy Number Variations - genetics; Epidermal growth factor receptors; Female; Genome, Human - genetics; Genomes; Humans; Lung cancer; Male; MDM2 protein; Metastases; Metastasis; Middle Aged; Mutation; Neoplasms - blood; Neoplasms - classification; Neoplasms - genetics; Neoplasms - pathology; Pleural Effusion - genetics; Proto-Oncogene Proteins c-mdm2 - genetics; Receptor, Epidermal Growth Factor - genetics; Regression analysis; TOR protein
• ISSN: 1535-7163; 1538-8514; 1538-8514
• DOI: 10.1158/1535-7163.MCT-16-0436

Collection of cell-free DNA (cfDNA) from the blood of individuals with cancer has permitted noninvasive tumor genome analysis. Detection and characterization of cfDNA in ascites and pleural effusions have not yet been reported. Herein, we analyzed cfDNA in the ascites and pleural effusions from six individuals with metastatic cancer. In all cases, cfDNA copy number variations (CNV) were discovered within the effusate. One individual had a relevant alteration with a high copy amplification in EGFR in a never smoker with lung cancer, who showed only MDM2 and CDK4 amplification in a prior tissue biopsy. Another subject with metastatic breast cancer had cytology-positive ascites and an activating PIK3CA mutation identified in the tissue, blood, and ascites collectively. This individual had tumor regression after the administration of the mTOR inhibitor everolimus and had evidence of chromotripsis from chromosomal rearrangements noted in the cell-free ascitic fluid. These results indicate that cfDNA from ascites and pleural effusions may provide additional information not detected with tumor and plasma cell-free DNA molecular characterization, and a context for important insights into tumor biology and clonal dynamic change within primary tumor and metastatic deposits. Mol Cancer Ther; 16(5); 948–55. ©2017 AACR.