Peer-reviewed by 2 reviewers with median rating of 14/20. Review process was triple-blinded.
Round 1 (13/20)
Round 2 (14/20)
Conceptual advance and Impact7
The authors present the interesting observation of the effects of PNA-clamps for NGS-based detection of rare mutations, an important issue for the early detection of resistant clones in oncology. The article is well written and appears convincing. Some more details are needed in the methods section.
The methods section is missing. Although the results sections gives many details of the procedure some of which could be trasnferred to the method section, some more information is needed. Especially the precise nature of the clamp is not described.
Conceptual advance and Impact4
This is a solid demonstration of potential use of PNA clamping for improving detection of a clinically relevant cancer driver mutation. It remains yet unclear how this change in detection sensitivity might impact therapy decisions
The authors should better explain why it is therapeutically relevant to detect KRAS mutations in lung cancer (i.e. how does this affect therapy decisions).
Results & Discussion
"Such a frequency would typically be challenging for reliable detection by NGS." The authors compare their method to NGS which is not routinely used for diagnostics. How would their method compare to currently available targeted methods to detect KRAS mutations ?