The mutREAD method detects mutational signatures from low quantities of cancer DNA

Abstract

Mutational processes acting on cancer genomes can be traced by investigating mutational signatures. Because high sequencing costs limit current studies to small numbers of good-quality samples, we propose a robust, cost- and time-effective method, called mutREAD, to detect mutational signatures from small quantities of DNA, including degraded samples. We show that mutREAD recapitulates mutational signatures identified by whole genome sequencing, and will ultimately allow the study of mutational signatures in larger cohorts and, by compatibility with formalin-fixed paraffin-embedded samples, in clinical settings.

Molekulare Tumordiagnostik als Triebfeder der Präzisionsonkologie

“…2000-3000 Gb bzw. [16][17][18][19][20] Reads. Die Reads stellen dabei das Ergebnis einer NGS-Analyse dar und bezeichnen kurze DNA-Sequenzen, die abhängig von der Probenaufbereitung und der eingesetzten Sequenziermethode in der Länge variieren können.…”

Therapeutic and prognostic insights from the analysis of cancer mutational signatures

“…What are the mechanisms underlying cell-intrinsic mutational signatures with potential therapeutic relevance? [91], further demonstrating the feasibility of analyzing mutational signatures in small-quantity samples such as cfDNA for prognostic purposes.…”

“…Whole-genome or whole-exome sequencing is often required to detect mutational signatures, and most cancer centers are not able to perform these assays for each patient. However, the emergence of reduced-representation approaches such as mutREAD [91] that substantially reduce cost, protocols for high-intensity sequencing of specific genomic regions [90], and the continual decrease of sequencing costs overall may make signature analysis within the clinic more commonplace in the future. Furthermore, it will also be of value to gain a mechanistic understanding of why certain mutational signatures are associated with different prognoses, such as whether the response to a specific therapy is affected by the biological process underlying a certain mutational signature.…”

Precision cancer medicine: Concepts, current practice, and future developments

“…To further increase the feasibility of integrating mutational signatures in clinical decision-making, considering that WGS is not yet established as clinical routine in most diagnostic units, alternative sequencing approaches might be required (e.g., Refs. [24,25]) or adapted targeted DNA panels appropriate also for formalin-fixed paraffinembedded tissue. Another intriguing aspect is whether mutational signatures can be robustly detected in cell-free DNA (cfDNA), with early reports suggesting that it may be possible [24,26].…”