In which group of patients you would send for RNAseq for translocations/fusions that might be missed by NGS in advanced NSCLC?

In patients who are never/rare smokers in whom tissue NGS is negative, I would strongly consider RNAseq of a recent or fresh biopsy. You can find the occult fusion (or missed MET) in about 15% of NGS negative, TMB low cases based on this recent very nice paper from MSKCC

https://www.ncbi.nlm.nih.gov/...

I would add young age to that list of characteristics, say 50 or less. There are many NTRK fusions which I understand, due to the many fusion partners, may be missed by DNA seq alone and with and an ever-increasing number of new rare translocations reported, my first choice now would also be an RNA ...

Interestingly, emerging targets such as NRG1 fusions (with different partners) were detected by RNAseq in the MSK paper cited by @Dr. First Last. This novel/emerging target has been most commonly reported in Lung mucinous adenocarcinoma histology and has been targeted with afatinib in various case r...

Frankly, my approach is to search until something is found. If a KRAS G12D is identified by DNA-based NGS, I am satisfied with the testing, but if no putative driver is identified at all, I strongly recommend RNA-based testing. Certain fusions, in particular, are prone to be missed by most DNA-based...