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Updated: May 26, 2025

Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
Comprehensive Survey of AACR GENIE Database of Tumor Mutation Burden (TMB) Among All Three Classes (I, II, III) of
Zhaohui Liao Arter1,2, Kevin Shieh1,2, Misako Nagasaka1,2
1Division of Hematology-Oncology, University of California Irvine School of Medicine, Orange, CA, USA.
Background:
BRAF mutations are generally divided into three classes based on the different altered mechanism of activation.
Methods:
We queried the public AACR GENIE database (version 13.1), which includes tumor mutation burden (TMB) data, to explore potential molecular differences among the three classes of non-small cell lung cancer (NSCLC).
Results:
Out of 20,713 unique NSCLC patients, 324 (1.6%) were BRAF mutations positive (BRAF+) class I, 260 (1.3%) class II, and 236 (1.1%) class III. The distribution of patient characteristics, including sex, age, and race, remains uniform across the three classes. The median TMB (mt/MB) was 6.5, 9.5, and 10.3 for class I, II, and III, respectively. The mean TMB was 61.5 ± 366.1 for class I, 40.5 ± 156.2 for class II, and 129.4 ± 914.8 for class III. About 30.5% of BRAF V600E+ patients had TMB ≥ 10; 47.7% of class II had TMB ≥ 10; and 52.5% of class III had TMB ≥ 10. For those patients with TMB ≥ 10, the median TMB was 45, 28.9, 18.4 for class I, II, and III, respectively. For TMB ≥ 10 patients, TP53 mutation was the most common co-alterations across all 3 classes.
Conclusion:
A substantial proportion of BRAF+ NSCLC patients exhibited a TMB ≥ 10, among all three classes of BRAF mutation classification, including BRAF V600E+ NSCLC. Class III mutations appeared to have the highest median TMB, followed by class II, and then class I.
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