Prevalence of RAF1 Aberrations in Metastatic Cancer Patients: Real-World Data

Sung Hee Lim; Jaeyun Jung; Jung Young Hong; Seung Tae Kim; Se Hoon Park; Joon Oh Park; Kyoung-Mee Kim; Jeeyun Lee

doi:10.3390/biomedicines11123264

Prevalence of RAF1 Aberrations in Metastatic Cancer Patients: Real-World Data

Biomedicines. 2023 Dec 9;11(12):3264. doi: 10.3390/biomedicines11123264.

Authors

Sung Hee Lim¹, Jaeyun Jung^{1

2}, Jung Young Hong¹, Seung Tae Kim¹, Se Hoon Park¹, Joon Oh Park¹, Kyoung-Mee Kim³, Jeeyun Lee¹

Affiliations

¹ Samsung Medical Center, Division of Hematology-Oncology, Department of Medicine, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea.
² Experimental Therapeutics Development Center, Samsung Medical Center, Seoul 06351, Republic of Korea.
³ Samsung Medical Center, Department of Pathology and Translational Genomics, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea.

Abstract

Purpose: Therapeutic targeting of RAF1 is a promising cancer treatment, but the relationship between clinical features and RAF1 aberrations in terms of the MAPK signaling pathway is poorly understood in various solid tumors.

Methods: Between October 2019 and June 2023 at Samsung Medical Center, 3895 patients with metastatic solid cancers underwent next-generation sequencing (NGS) using TruSight Oncology 500 (TSO500) assays as routine clinical practice. We surveyed the incidence of RAF1 aberrations including mutations (single-nucleotide variants [SNVs]), amplifications (copy number variation), and fusions.

Results: Among the 3895 metastatic cancer patients, 77 (2.0%) exhibited RAF1 aberrations. Of these 77 patients, 44 (1.1%) had RAF1 mutations (SNV), 25 (0.6%) had RAF1 amplifications, and 10 (0.3%) had RAF1 fusions. Among the 10 patients with RAF1 fusions, concurrent RAF1 amplifications and RAF1 mutations were detected in one patient each. The most common tumor types were bladder cancer (11.5%), followed by ampulla of Vater (AoV) cancer (5.3%), melanoma (3.0%), gallbladder (GB) cancer (2.6%), and gastric (2.3%) cancer. Microsatellite instability high (MSI-H) tumors were observed in five of 76 patients (6.6%) with RAF1 aberrations, while MSI-H tumors were found in only 2.1% of patients with wild-type RAF1 cancers (p < 0.0001).

Conclusion: We demonstrated that approximately 2.0% of patients with metastatic solid cancers have RAF1 aberrations according to NGS of tumor specimens.

Keywords: RAF inhibitor; RAF1 aberration; amplification; fusion; single-nucleotide variants.

Grants and funding

This research was supported by the [Bio&Medical Technology Development Program] of the National Research Foundation (NRF) funded by the Korean Government (MSIT) (No RS-2023-00222838).