Using cell‐free RNA to identify B‐ and T‐cell clonality for diagnosis and monitoring of B‐ and T‐cell neoplasms

Cell‐free RNA (cfRNA) is emerging as a supplemental approach for liquid biopsy (LBx). Given that lymphoid cells and plasma cells express substantial quantities of immunoglobulin (Ig) and T‐cell receptor (TCR) RNA, we investigated the utility of using cfRNA for detecting B‐cell and T‐cell clonality in LBxs. Using next‐generation sequencing (NGS) of cfRNA, we clonotyped Igs and TCRs in LBx samples from patients with B‐cell neoplasm, T‐cell neoplasm, myeloid neoplasm and solid tumors alongside cancer‐free individuals. To establish a clonality cutoff, we clonotyped tissue RNA from patients with confirmed clonal B‐ or T‐cell and from polyclonal. Clonotype‐naïve testing of LBx samples demonstrated B‐cell clonality in 36% of B‐cell neoplasms, 7% of normal, 8% of T‐cell lymphomas, 13% of myeloid neoplasms, and 14% of solid tumors. T‐cell clonality using TCR beta or gamma demonstrated T‐cell clonality in 22% of T‐cell neoplasms, 3% of normal, 5% of myeloid neoplasms, 7% of solid tumors and 3% of B‐cell neoplasms. This confirms that Clonotype‐naïve cfRNA testing in LBx is a reliable approach for detecting B‐ and T‐cell clonality.