Mosaic BRAF fusions are a recurrent cause of congenital melanocytic naevi targetable by MEK inhibition

Alicia’s citation:
Martin SB#, Polubothu S#, Bruzos AL# et al. 2023. “Mosaic BRAF fusions are a recurrent cause of congenital melanocytic naevi targetable by MEK inhibition.” The Journal of Investigative Dermatology,144(3):593-600. doi: 10.1016/j.jid.2023.06.213 (#equal contribution). IF(2021) = 7.590.

All authors citation:
Martin SB#, Polubothu S#, Bruzos AL#, Kelly G, Horswell S, Sauvadet A, Bryant D, Zecchin D, Riachi M, Michailidis F, Sadri A, Muwanga-Nanyonjo N, Lopez-Balboa P, Knöpfel N, Bulstrode N, Pittman A, Yeh I, Kinsler V. (2023) “Mosaic BRAF fusions are a recurrent cause of congenital melanocytic naevi targetable by MEK inhibition.” The Journal of Investigative Dermatology, 144(3):593-600. DOI: 10.1016/j.jid.2023.06.213 IF(2021) = 7.590 (#equal contribution)

About the paper:

Scope: We studied a subset of 169 children with multiple congenital melanocytic naevi (CMN), that were wild-type for NRAS/BRAF mutations. We revealed and validated recurrent mosaic BRAF fusions and RAF1 fusions that involved the loss of the 5’ regulatory domain of BRAF/RAF1 but preserved the kinase domain. Due to the relation with MAPK hyperactivation, trametinib was tested in vitro and in two patients showing promising results. Impact: Previously known recurrent causes of CMN are mosaic heterozygous missense pathogenic variants in NRAS (68% cases) and BRAF (7% cases) with 25% of patients with an unknown cause. This research reveals recurrent mosaic gene fusions as a mechanism and identifies trametinib as a promising treatment option. My contribution: I was involved in the bioinformatic analysis of mosaic gene fusions. Personal importance: This first-author publication of my postdoc in the United Kingdom marks my independence from my thesis supervisor’s guidance.

Authorship:
Position of AL Bruzos: 3
Total number of authors: 18
Authors: Sara Barberan Martin; Satyamaanasa Polubothu; Alicia Lopez Bruzos; Gavin Kelly; Stuart Horswell; Aimie Sauvadet; Dale Bryant; Davide Zecchin; Melissa Riachi; Fanourios Michailidis; Amir Sadri; Noreen Muwanga-Nanyonjo; Pablo Lopez-Balboa; Nicole Knöpfel; Neil Bulstrode; Alan Pittman; Iwei Yeh; Veronica Kinsler

Journal information
ISSN: 0022-202X
eISSN: 1523-1747
Current Publisher: ELSEVIER SCIENCE INC, STE 800, 230 PARK AVE, NEW YORK, USA, NY, 10169

Journal Impact Factor (JIF)
-JIF: 7.590 (2021)
-JIF Rank: 5/68 (2021)
-JIF Quartile: Q1 (2021)
Journal Citation Indicator (JCI)
-JCR Category: DERMATOLOGY
-JCR Category Rank: 6/70
-JCR Category Quartile: Q1

Peer-review process:
Received: 1 February 2023
Accepted: 16 May 2023
Published: 18 September 2023