Saliva-derived DNA is suitable for the detection of clonal haematopoiesis of indeterminate potential

Abstract

Clonal haematopoiesis of indeterminate potential (CHIP) has been associated with many adverse health outcomes. However, further research is required to understand the critical genes and pathways relevant to CHIP subtypes, evaluate how CHIP clones evolve with time, and further advance functional characterisation and therapeutic studies. Large epidemiological studies are well placed to address these questions but often collect saliva rather than blood from participants. Paired saliva- and blood-derived DNA samples from 94 study participants were sequenced using a targeted CHIP-gene panel. The ten genes most frequently identified to carry CHIP-associated variants were analysed. Fourteen unique variants associated with CHIP, ten in DNMT3A, two in TP53 and two in TET2, were identified with a variant allele fraction (VAF) between 0.02 and 0.2 and variant depth ≥ 5 reads. Eleven of these CHIP-associated variants were detected in both the blood- and saliva-derived DNA sample. Three variants were detected in blood with a VAF > 0.02 but fell below this threshold in the paired saliva sample (VAF 0.008-0.013). Saliva-derived DNA is suitable for detecting CHIP-associated variants. Saliva can offer a cost-effective biospecimen that could both advance CHIP research and facilitate clinical translation into settings such as risk prediction, precision prevention, and treatment monitoring.

Keywords: Blood; CHIP; Clonal haematopoiesis; Next generation sequencing; Saliva; Somatic mutations.

Figure 1

A graphic representation of our bioinformatic workflow used in this study to identify somatic variants (VAFs 0.02–0.2) in blood and saliva-derived DNA pairs. Three CHIP-associated variants detect in blood only, indicated by *, were detected in the saliva-derived DNA pair after exploring below the VAF threshold 0.02 (ranging between 0.008—0.013).