Analysis of quality metrics in comprehensive cancer genomic profiling using a dual DNA-RNA panel.

Background

The nucleic acid quality from formalin-fixed paraffin-embedded (FFPE) tumor vary among samples, resulting in substantial variability in the quality of comprehensive cancer genomic profiling tests. The objective of the study is to investigate how nucleic acid quality affects sequencing quality. We also examined the variations in nucleic acid quality among different hospitals or cancer types.

Methods

Three nucleic acid quality metrics (ddCq, Q-value, and DV200) and five sequencing quality metrics (on-target rate, mean depth, coverage uniformity, target exon coverage, and coverage of the housekeeping gene) were examined using 585 samples from the Todai OncoPanel, a dual DNA-RNA panel.

Results

In the DNA panel, ddCq served as an indicator of sequencing depth and Q-value reflected the uniformity of sequencing across different regions. It was essential to have favorable values not only for ddCq but also for Q-value to obtain ideal sequencing results. For the RNA panel, DV200 proved to be a valuable metric for assessing the coverage of the housekeeping genes. Significant inter-hospital differences were observed for DNA quality (ddCq and Q-value), but not for RNA quality (DV200). Differences were also observed among cancer types, with Q-value being the lowest in lung and the highest in cervix, while DV200 was the highest in lung and the lowest in bowel.

Conclusions

We demonstrated distinct characteristics and high predictive performances of ddCq, Q-value, and DV200. Variations were observed in the nucleic acid quality across hospitals and cancer types. Further study is warranted on preanalytical factors in comprehensive cancer genomic profiling tests.

Informations de copyright

© 2024 The Authors.

Déclaration de conflit d'intérêts

The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Shinji Kohsaka reports financial support was provided by Konica Minolta Inc. Hidenori Kage reports financial support was provided by Konica Minolta Inc. Hiroyuki Aburatani reports financial support was provided by Konica Minolta Inc. Hiroyuki Aburatani reports financial support was provided by Chugai Pharmaceutical Co Ltd. Hiroyuki Mano reports financial support was provided by Konica Minolta Realm. Katsutoshi Oda reports financial support was provided by Konica Minolta Inc. Katsutoshi Oda reports financial support was provided by Chugai Pharmaceutical Co Ltd. Hiroyuki Mano reports a relationship with Daiichi Sankyo Inc that includes: funding grants. Hiroyuki Mano reports a relationship with PFDeNA that includes: funding grants. Hiroyuki Mano reports a relationship with Ambry Genetics Corp that includes: funding grants. Hiroyuki Mano reports a relationship with Ono Pharmaceutical Co Ltd that includes: funding grants. Hiroyuki Mano reports a relationship with CureGene that includes: board membership. Katsutoshi Oda reports a relationship with AstraZeneca Pharmaceuticals LP that includes: funding grants and speaking and lecture fees. Katsutoshi Oda reports a relationship with Takeda Pharmaceutical Company Limited that includes: funding grants and speaking and lecture fees. Shinji Kohsaka has patent pending to The University of Tokyo. Hiroyuki Mano has patent pending to The University of Tokyo. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.