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Molecular testing techniques for targetable alterations in non-small cell lung cancer (NSCLC)

Molecular testing techniques for targetable alterations in non-small cell lung cancer (NSCLC)
  Tissue PCR sequencing Tissue allele specific PCR sequencing Tissue FISH Tissue IHC Tissue NGS ctDNA PCR ctDNA NGS Tissue RNA
EGFR
(sensitizing and T790M)
+ ++ 0 0 ++ + + +
HER2 mutation + ++ 0 0 ++ + + +
METex14 mutation 0 ++ 0 0 ++ + + ++
BRAF mutation + ++ 0 0 ++ + + +
KRAS mutation + ++ 0 0 ++ + + +
ALK rearrangement 0 0 ++ ++ + + + ++
ROS1 rearrangement 0 0 ++ 0 + 0 + ++
MET amplification 0 0 ++ 0 + 0 + +
RET rearrangement 0 0 ++ 0 + + + ++
PD-L1 protein expression 0 0 0 ++ 0 0 0 0
NTRK fusion 0 0 ++ + + 0 + ++
NRG1 fusion 0 0 ++ + + 0 + ++
++: Highest sensitivity.
+: Lower sensitivity (higher chance of false negative).
0: Not useful.
EGFR: epidermal growth factor receptor; HER2: human epidermal growth factor receptor 2; ALK: anaplastic lymphoma kinase; PCR: polymerase chain reaction; PD-L1: programmed cell death-ligand 1; NTRK: neurotrophic receptor tyrosine kinase; NRG1: neuregulin 1; FISH: fluorescence in situ hybridization; IHC: immunohistochemistry; NGS: next generation sequencing; ctDNA: circulating tumor DNA.
* FISH is highly sensitive but not recommended due to low yield and no approved targeted therapy.
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