Cell-Free DNA from Ascites and Pleural Effusions: Molecular Insights into Genomic Aberrations and Disease Biology. Mol Cancer Ther 2017 May;16(5):948-955
Date
05/05/2017Pubmed ID
28468865DOI
10.1158/1535-7163.MCT-16-0436Scopus ID
2-s2.0-85020053681 (requires institutional sign-in at Scopus site) 75 CitationsAbstract
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.
Author List
Husain H, Nykin D, Bui N, Quan D, Gomez G, Woodward B, Venkatapathy S, Duttagupta R, Fung E, Lippman SM, Kurzrock RAuthor
Razelle Kurzrock MD Center Associate Director, Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdultAged
Aged, 80 and over
Ascites
Cell Line, Tumor
Cell-Free Nucleic Acids
Class I Phosphatidylinositol 3-Kinases
Cyclin-Dependent Kinase 4
DNA Copy Number Variations
ErbB Receptors
Female
Genome, Human
Humans
Male
Middle Aged
Mutation
Neoplasms
Pleural Effusion
Proto-Oncogene Proteins c-mdm2
