High prevalence of clonal hematopoiesis-type genomic abnormalities in cell-free DNA in invasive gliomas after treatment. Int J Cancer 2021 Jun 01;148(11):2839-2847
Date
01/27/2021Pubmed ID
33497479Pubmed Central ID
PMC8048515DOI
10.1002/ijc.33481Scopus ID
2-s2.0-85100514305 (requires institutional sign-in at Scopus site) 19 CitationsAbstract
Plasma cell-free DNA (cfDNA) is emerging as an important diagnostic tool in cancer. However, cfDNA alterations may differ from those in tissue and sometimes may reflect processes unrelated to the cancer, including clonal hematopoiesis (CH). We examined plasma cfDNA, tested by next-generation sequencing (NGS), for characterized alterations (excluding variants of unknown significance) in 135 patients with invasive glioma. Overall, 21% (28/135) had ≥1 alteration; 17% (23/135) had CH-type cfDNA mutations. Temozolomide (a mutagenic alkylating agent) with concurrent radiation therapy prior to blood draw was significantly associated with an increase in CH-type mutations, even after age, race/ethnicity, and WHO-grade were considered as confounders (odds ratio [95% confidence interval, CI] 8.98 [1.13-71.46]; P = .04; multivariable analysis). Further, of 18 patients with invasive glioma who had both cfDNA and tissue DNA NGS and had ≥1 cfDNA alteration, 16 (89%) had ≥1 cfDNA alteration not found in their tissue DNA, including CH-type alterations in genes such as TP53 (most common), ATM, GNAS, and JAK2. Altogether, 87% of cfDNA alterations (20/23) observed in the 18 patients were implicated in CH. Finally, examining all 135 patients, CH-type cfDNA mutations were an independent prognostic factor for shorter survival (hazard ratio [95% CI] 3.28 [1.28-8.40]; P = .01). These findings emphasize that not all characterized cfDNA alterations detected in patients with solid tumors are cancer-related. Importantly, in patients with invasive gliomas who have had prior temozolomide and radiation, CH-related alterations in cfDNA are frequent and correlate with poor outcomes.
Author List
Okamura R, Piccioni DE, Boichard A, Lee S, Jimenez RE, Sicklick JK, Kato S, 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
Brain Neoplasms
Cell-Free Nucleic Acids
Chemoradiotherapy
DNA, Neoplasm
Glioma
High-Throughput Nucleotide Sequencing
Humans
Male
Middle Aged
Mutation
Prognosis
Sequence Analysis, DNA
Survival Analysis
Treatment Outcome
Young Adult
