Table 2.

Summary of the investigated mechanisms of acquired resistance

Mutations detected by NGS
IDTumor contentAcquired mutationMutant allelesMutant alleles normalized fortumor contentHSFounder mutations (mutant alleles; normalized for tumor content; HS)HER2 IHCHER2 AmplificationaMET IHC (H-score)MET Amplificationa
130%KRAS Q61H11%37%74TP53 R213Stop (27%; 90%; 180)2+No200No
22+Yes0No
390%BRAF V600E13%14%28TP53 R249W (60%; 67%, 134)1+No0No
42+No300Yes
570%KRAS Q61K4%6%12TP53 R248Q (56%; 80%; 160) SMAD4 (63%; 90%; 180)2+bNoc180No
650%KRAS G12R17%34%68APC L1488Stop (19%; 38%; 76) TP53 G187Stop (37%; 74%; 148)NDNoNANo
71+No180No
83+Yes180No
92+No120No
102+No100No
112+No120Yes
122+Yes120No
132+NoNANo
142+No40No
1580%AKT1 D46N18%22%44TP53 R282W (14%;17%; 34)2+No30Nod
1665%KRAS Q61H36%55%110TP53 P278S (52%; 80%; 160) ATM P3050 (49%; 75%; 150)2+No300Yes
1770%BRAF V600E5%7%14TP53 L265P (40%; 57%; 114) TP53 E171G (24%; 34%; 68)2+bNo210No
1875%KRAS G12R9%12%24TP53 D281E (58%; 77%; 154)1+No120No
1930%KRAS G13D6%20%40SMAD4 Q75STOP (20%; 66%; 132) GNAS R201H (15%; 50%; 100)NDNo0No
202+No300Yes
211+No180No
2240%KRAS G12V32%53%106TP53 D281 (22%; 36%; 72)1+No180No
  • Abbreviations: HS, heterogeneity score; NA, not available.

  • aAmplification status is assessed by SISH.

  • bPresence of a small area (<10%) with 3+ expression.

  • cPresence of <10% cells with HER2 amplification.

  • dPresence of <10% cells with MET amplification.