Comprehensive Survey of AACR GENIE Database of Tumor Mutation Burden (TMB) Among All Three Classes (I, II, III) of BRAF Mutated (BRAF+) NSCLC

Zhaohui Liao Arter,1,2 Kevin Shieh,1,2 Misako Nagasaka,1,2 Sai-Hong Ignatius Ou1,2 1Division of Hematology-Oncology, University of California Irvine School of Medicine, Orange, CA, USA; 2Chao Family Comprehensive Cancer Center, Orange, CA, USACorrespondence: Sai-Hong Ignatius Ou, Division of Hematology-Oncology, University of California Irvine School of Medicine, Orange, CA, USA, Tel +1 714-456-5153, Fax +1 714-456-2242, Email [email protected]: 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.Keywords: target therapy, immunocheck point inhibitor (ICI), BRAF mutation, tumor mutation burden (TMB), class I, II, III mutations, NSCLC