High-throughput sequencing for noninvasive disease detection in hematologic malignancies

Abstract

Noninvasive monitoring of minimal residual disease (MRD) has led to significant advances in personalized management of patients with hematologic malignancies. Improved therapeutic options and prolonged survival have further increased the need for sensitive tumor assessment that can inform treatment decisions and patient outcomes. At diagnosis or relapse of most hematologic neoplasms, malignant cells are often easily accessible in the blood as circulating tumor cells (CTCs), making them ideal targets to noninvasively profile the molecular features of each patient. In other cancer types, CTCs are generally rare and noninvasive molecular detection relies on circulating tumor DNA (ctDNA) shed from tumor deposits into circulation. The ability to precisely detect and quantify CTCs and ctDNA could minimize invasive procedures and improve prediction of clinical outcomes. Technical advances in MRD detection methods in recent years have led to reduced costs and increased sensitivity, specificity, and applicability. Among currently available tests, high-throughput sequencing (HTS)–based approaches are increasingly attractive for noninvasive molecular testing. HTS-based methods can simultaneously identify multiple genetic markers with high sensitivity and specificity without individual optimization. In this review, we present an overview of techniques used for noninvasive molecular disease detection in selected myeloid and lymphoid neoplasms, with a focus on the current and future role of HTS-based assays.

T-cell receptor αβ chain pairing is associated with CD4+ and CD8+ lineage specification

“…Our results thus provide new evidence for the role of germline-encoded TCR-pMHC interactions and implicate both chains as playing important roles in determining TCR interactions. We believe that the rigorous examination of the normal TCR repertoires presented in this study both demonstrates the utility of capturing αβ pairs in profiling the TCR repertoire and will prove to be valuable in understanding the perturbations caused by infectious, oncological and auto-immune disease states [47][48][49][50][51][52][53] .…”

Genomic profiling of plasma circulating tumor DNA reveals genetics and residual disease in extranodal NK/T-cell lymphoma

“…Plasma cfDNA includes tumor cell-derived plasma ctDNA and normal cell apoptosis-derived cfDNA, which are DNA fragments. ctDNA could be a more comprehensive reflection of gene mutations in all tumors than conventional biopsy (Herrera & Armand, 2017;Scherer et al, 2017). Therefore, ctDNA-based detection methods are critical for identifying which mutation is tumor-specific.…”

Myeloproliferative neoplasms: Diagnostic workup of the cythemic patient

“…The increasing use of molecular and cytogenetic tools in hematopoietic disorders has led to a significant improvement in diagnostic and prognostic accuracy in MPN. Although there is wide variability and discretion in the depth and breadth of a molecular diagnostic workup, this discussion focuses on the minimal testing required for MPN diagnosis and classification …”