Table 2.

Molecular analysis of rebiopsy samples of evaluable patients

Mechanisms of resistance
Patient no.ALK FISHALK FISH CNGALK domain sequenceaEGFRKRAS
4PositiveNegativeL1196MWTaWTa
5PositiveNegativeL1196MWTaWTa
6PositiveNegativeG1269AbWTa,cWTa,c
7PositivePositiveG1269AWTcWTc
8PositivePositiveWTWTaWTa
9aNegativeNegativeNAL858Ra,cWTa,c
9bPositiveNegativeWTbWTcWTc
10dPositive/negativeeNegativeWTNDG12Cc,e
11PositiveNegativeWTWTaG12Va
12NegativeNegativeWTWTcWTc
13dPositiveNegativeWTbNDND
14PositiveNegativeWTWTaWTa

NOTE: Bold text denotes the key mechanism(s) of resistance.

Abbreviations: NA, not available; WT, wild-type.

  • aDirect sequencing.

  • bHeterozygous for rs3795850 ALK SNP.

  • cSNaPshot includes APC, AKT1, BRAF, CTNNB1, EGFR, FLT3, JAK2, KIT, KRAS, MAP2K1 (MEK1), NOTCH1, NRAS, PIK3CA, PTEN, and TP53.

  • dPatients with intrinsic resistance.

  • eFrom patient-derived cell line with loss of ALK gene rearrangement by FISH or RT-PCR. The FFPE tissue was ALK FISH+.