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Case Reports
. 2018 Aug;13(8):e131-e133.
doi: 10.1016/j.jtho.2018.03.026. Epub 2018 Apr 6.

An Acquired NRAS Q61K Mutation in BRAF V600E-Mutant Lung Adenocarcinoma Resistant to Dabrafenib Plus Trametinib

Daniel L Abravanel  1 , Mizuki Nishino  2 , Lynette M Sholl  3 , Chiara Ambrogio  1 , Mark M Awad  4
Affiliations
Case Reports

An Acquired NRAS Q61K Mutation in BRAF V600E-Mutant Lung Adenocarcinoma Resistant to Dabrafenib Plus Trametinib

Daniel L Abravanel et al. J Thorac Oncol. 2018 Aug.
No abstract available

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Conflict of interest statement

Conflict of interest statement:

Dr. Abravanel has nothing to disclose.

Dr. Nishino reports personal fees from WorldCare Clinical, Toshiba Medical Systems, and Daiichi Sankyo; grants from Merck, Toshiba Medical Systems, AstraZeneca and the NIH; and, personal fees from Bayer and Roche, all outside the submitted work.

Dr. Sholl has nothing to disclose.

Dr. Ambrogio has nothing to disclose.

Dr. Awad has nothing to disclose.

Figures

Figure 1:
Figure 1:
Computed tomography imaging shows initial response to combination dabrafenib and trametinib and subsequent progression A. CT scan of the chest at baseline prior to dabrafenib plus trametinib therapy demonstrated a dominant consolidated mass (asterisk) in the right lower lobe with heterogenous CT density and invasion into the right atrium (arrowhead), and right hilar and subcarinal lymphadenopathy (arrows). B. CT scan at 13 weeks of therapy demonstrated a marked response to therapy with significant decrease of the dominant mass (asterisk) and lymph nodes (arrows). C. CT scan at 21 weeks of therapy demonstrated continued response in the dominant right lower lobe lesion (asterisk) but progressive disease with increased bilateral hilar and subcarinal lymphadenopathy (arrows), multiple new lung nodules (arrowheads) and a new left chest wall nodule (large arrow).
Figure 2:
Figure 2:
Tumor and cell-free DNA sequencing at diagnosis and after progression on combination dabrafenib and trametinib shows acquisition of an NRAS Q61K mutation A. Aligned sequencing reads from a pre-treatment tumor biopsy (top) detected a BRAF c. 1799T>A point mutation (p.V600E); sequencing of a repeat biopsy after progression on combination dabrafenib and trametinib (bottom) demonstrated persistence of the BRAF 1799T>A mutation and the acquisition of a NRAS c.181C>A point mutation (p.Q61K). B. Commercial plasma genotyping also detected BRAF V600E in both pre-treatment and post-treatment samples, but NRAS Q61K was only detected after progression on combination dabrafenib and trametinib.s
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