TY - JOUR
T1 - Evaluation of the Oncomine Pan-Cancer Cell-Free Assay for Analyzing Circulating Tumor DNA in the Cerebrospinal Fluid in Patients with Central Nervous System Malignancies
AU - Shah, Mauli
AU - Takayasu, Takeshi
AU - Zorofchian Moghadamtousi, Soheil
AU - Arevalo, Octavio
AU - Chen, Melissa
AU - Lan, Chieh
AU - Duose, Dzifa
AU - Hu, Peter
AU - Zhu, Jay Jiguang
AU - Roy-Chowdhuri, Sinchita
AU - Riascos, Roy F.
AU - Chen, Hui
AU - Luthra, Rajyalakshmi
AU - Esquenazi, Yoshua
AU - Ballester, Leomar Y.
N1 - Funding Information:
Supported by the National Cancer Institute , NIH, award K08CA241651 (L.Y.B.).
Publisher Copyright:
© 2021 Association for Molecular Pathology and American Society for Investigative Pathology
PY - 2021/2
Y1 - 2021/2
N2 - Available tools to evaluate patients with central nervous system (CNS) tumors such as magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) cytology, and brain biopsies, have significant limitations. MRI and CSF cytology have poor specificity and sensitivity, respectively, and brain biopsies are invasive. Circulating tumor DNA in CSF (CSF-ctDNA) could be used as a biomarker in patients with CNS tumors, but studies in this area are limited. We evaluated four CSF-ctDNA extraction methods and analyzed mutations in CSF-ctDNA with the Oncomine Pan-Cancer cell-free assay. CSF-ctDNA was extracted from 38 patients with primary or metastatic CNS tumors and 10 patients without CNS malignancy. Commercial ctDNA controls were used for assay evaluation. CSF-ctDNA yields ranged from 3.65 to 3120 ng. Mutations were detected in 39.5% of samples. TP53 was the most commonly mutated gene and copy number alterations were detected in CCND1, MYC, and ERBB2/HER2. Twenty-five percent of CSF-cytology–negative samples showed mutations in CSF-ctDNA. There was good concordance between mutations in CSF-ctDNA and matching tumors. The QIAamp Circulating Nucleic Acid Kit was the optimal method for extraction of CSF-ctDNA and the Oncomine cell-free DNA assay is suitable for detection of mutations in CSF-ctDNA. Analysis of CSF-ctDNA is more sensitive than CSF-cytology and has the potential to improve the diagnosis and monitoring of patients with CNS tumors.
AB - Available tools to evaluate patients with central nervous system (CNS) tumors such as magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) cytology, and brain biopsies, have significant limitations. MRI and CSF cytology have poor specificity and sensitivity, respectively, and brain biopsies are invasive. Circulating tumor DNA in CSF (CSF-ctDNA) could be used as a biomarker in patients with CNS tumors, but studies in this area are limited. We evaluated four CSF-ctDNA extraction methods and analyzed mutations in CSF-ctDNA with the Oncomine Pan-Cancer cell-free assay. CSF-ctDNA was extracted from 38 patients with primary or metastatic CNS tumors and 10 patients without CNS malignancy. Commercial ctDNA controls were used for assay evaluation. CSF-ctDNA yields ranged from 3.65 to 3120 ng. Mutations were detected in 39.5% of samples. TP53 was the most commonly mutated gene and copy number alterations were detected in CCND1, MYC, and ERBB2/HER2. Twenty-five percent of CSF-cytology–negative samples showed mutations in CSF-ctDNA. There was good concordance between mutations in CSF-ctDNA and matching tumors. The QIAamp Circulating Nucleic Acid Kit was the optimal method for extraction of CSF-ctDNA and the Oncomine cell-free DNA assay is suitable for detection of mutations in CSF-ctDNA. Analysis of CSF-ctDNA is more sensitive than CSF-cytology and has the potential to improve the diagnosis and monitoring of patients with CNS tumors.
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U2 - 10.1016/j.jmoldx.2020.10.013
DO - 10.1016/j.jmoldx.2020.10.013
M3 - Article
C2 - 33531134
AN - SCOPUS:85099906857
SN - 1525-1578
VL - 23
SP - 171
EP - 180
JO - Journal of Molecular Diagnostics
JF - Journal of Molecular Diagnostics
IS - 2
ER -