(P 103) BRAF MUTATIONS AND CONCURRENT ALTERATIONS IN PATIENTS WITH SOFT TISSUE SARCOMA

Author(s)

Hiroshi Kobayashi, MD, PhD

Associate professor/Lecturer
The University of Tokyo Hospital
Bunkyo-ku, Tokyo, Japan

Co-Author(s)

LZ

Liuzhe Zhang, MD

Fellow
University Musculoskeletal Oncology Unit, Mount Sinai Hospital, Department of Surgery, University of Toronto, Toronto, Canada
Toronto, Tokyo, Japan
KO

Koichi Okajima, MD

The University of Tokyo, Department of Orthopaedic Surgery
Bunkyo-ku, Tokyo, Japan
YI

Yuki Ishibashi, MD

The University of Tokyo, Department of Orthopaedic Surgery
Bunkyo-ku, Tokyo, Japan
Toshihide Hirai

clinician
National Cancer Center Institute
Tokyo, Tokyo, Japan
YT

Yusuke Tsuda, N/A, MD, Ph.D

The University of Tokyo
Tokyo, Tokyo, Japan
MI

Masachika Ikegami, MD/PhD

Trainee
Division of Cellular Signaling, National Cancer Center Research Institute
Chuo-ku, Tokyo, Japan
HK

Hidenori Kage, MD, PhD

The University of Tokyo, Department of Respiratory Medicine
Bunkyo-ku, Tokyo, Japan
AS

Aya Shinozaki-Ushiku, MD, PhD

The University of Tokyo, Division of Integrative Genomics
Bunkyo-ku, Tokyo, Japan
KO

Katsutoshi Oda, MD, PhD

The University of Tokyo, Division of Integrative Genomics
Bunkyo-ku, Tokyo, Japan
ST

Sakae Tanaka, N/A, MD, PhD

The University of Tokyo Hospital
Bunkyo-ku, Tokyo, Japan

Objective: BRAF alterations, including V600E and non-V600E mutations and fusions, in soft tissue sarcoma (STS) have been identified in a limited case series. Here, we aimed to evaluate the frequency of BRAF mutations and concurrent alterations in STS to understand their therapeutic action.

Methods: In this retrospective analysis, we included data from 1,964 patients with advanced STS who underwent comprehensive genomic profiling tests at hospitals in Japan between June 2019 and March 2023. The prevalence of BRAF and recurrent concurrent gene alterations were also investigated.

Results: BRAF mutations were detected in 24 (1.2%) of 1,964 STS patients, with a median age of 47 (range 1–69) years. BRAF V600E was detected in 11 (0.6%) of the 1,964 patients with STS, BRAF non-V600E mutations in 9 (4.6%), and BRAF fusions were detected in 4 (0.2%). BRAF V600E was identified in 4 (0.2%) cases of malignant peripheral nerve sheath tumors. The most common concurrent alteration was CDKN2A (11 cases, 45.8%), and the frequency was equivalent to that of the BRAF V600E (5/11 cases, 45.5%) and non-V600E (5/9 cases, 55.6%) groups. Recurrent concurrent alterations, such as TERT promoter mutations (7 cases, 29.2%), were detected at the same frequency in the V600E and non-V600E groups. In contrast, TP53 alterations (4/9 cases, 44.4%) and mitogen-activated protein kinase (MAPK)-activating genes, including NF1, GNAQ, and GNA11 (3/9 cases, 33.3%), were identified as relatively higher in the non-V600E group than in the V600E group (each 1/11 case, 9.1%).

Conclusion: We identified BRAF alterations at a rate of 1.2% in all patients with advanced STS. Among them, BRAF V600E and BRAF fusions account for 45.8% and 16.7%, respectively. Collectively, our findings support the clinical characteristics and therapeutic strategies for patients with BRAF-altered advanced STS.