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. 2024 May 9;25(10):5183.
doi: 10.3390/ijms25105183.

BRAF Mutations in Patients with Myeloid Neoplasms: A Cancer Center Multigene Next-Generation Sequencing Analysis Experience

Fei Fei  1 , Caitlin Caporale  2 , Lisa Chang  1 , Barbara K Fortini  3 , Haris Ali  4 , Diana Bell  5 , Anthony Stein  4 , Guido Marcucci  4 , Milhan Telatar  1 , Michelle Afkhami  1
Affiliations

BRAF Mutations in Patients with Myeloid Neoplasms: A Cancer Center Multigene Next-Generation Sequencing Analysis Experience

Fei Fei et al. Int J Mol Sci. .

Abstract

BRAF mutations are rare in myeloid neoplasms and are reported to be associated with poor treatment outcomes. The purpose of our study is to characterize BRAF mutations in myeloid neoplasms using a next-generation sequencing (NGS) panel based on the experiences of a single cancer center. We conducted a retrospective review of patients with myeloid neoplasms who underwent the HopeSeq studies between January 2018 and September 2023. A total of 14 patients with myeloid neoplasms carrying BRAF mutations were included in our cohort. The clinical, pathological, and molecular features of these patients were investigated. Our study indicates that BRAF mutations are rare in myeloid neoplasms, constituting only 0.53% (14/2632) of all myeloid neoplasm cases, with the most common BRAF mutation being BRAF V600E (4/14; 28.6%). Interestingly, we observed that six out of seven patients with acute myeloid leukemia (AML) exhibited AML with monocytic differentiation, and all the patients with AML exhibited an extremely poor prognosis compared to those without BRAF mutations. TET2 (5/14; 35.7%), ASXL1 (4/14; 28.6%), and JAK2 (4/14; 28.6%) were the three most frequently co-mutated genes in these patients. Moreover, we noted concurrent KMT2A gene rearrangement with BRAF mutations in three patients with AML (3/7; 42.9%). Our study suggests that although BRAF mutations are rare in myeloid neoplasms, they play a crucial role in the pathogenesis of specific AML subtypes. Furthermore, RAS pathway alterations, including BRAF mutations, are associated with KMT2A gene rearrangement in AML. However, these findings warrant further validation in larger studies.

Keywords: BRAF mutation; myeloid neoplasms; next-generation sequencing.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
BRAF mutations in patients with myeloid neoplasms (n = 14).
Figure 2
Figure 2
Pathogenic/likely pathogenic mutations identified in myeloid neoplasms with BRAF mutations (n = 14).
Figure 3
Figure 3
Pathogenic/likely pathogenic mutations identified in AML patients with KMT2A gene rearrangements (n = 77).
Figure 4
Figure 4
Overall survival between AML patients with or without BRAF mutations.
See this image and copyright information in PMC

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Grants and funding

This research received no external funding.
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