In:
Pigment Cell & Melanoma Research, Wiley, Vol. 31, No. 3 ( 2018-05), p. 432-436
Abstract:
BRAF and MEK inhibitors have improved clinical outcomes in advanced, BRAF V 600 ‐mutated melanomas. Acquired resistance occurs in most patients, with numerous and diverse drivers. We obtained pretreatment and progression biopsies from a patient who progressed on dabrafenib and trametinib. In addition to a preserved BRAF V 600E mutation, an internal deletion (rearrangement) of BRAF was observed in the progression sample. This deletion involved exons 2–8, which includes the Ras‐binding domain, and is analogous to previously documented BRAF fusions and splice variants known to reactivate RAS ‐ RAF ‐ MEK ‐ ERK signaling. In a large cohort of melanomas, 10 additional internal deletions were identified (0.4% of all melanomas; nine of which had concurrent BRAF mutations), as well as sporadically in other tumor types. Thus, we describe a novel mechanism of resistance to BRAF and MEK inhibition.
Type of Medium:
Online Resource
ISSN:
1755-1471
,
1755-148X
DOI:
10.1111/pcmr.2018.31.issue-3
Language:
English
Publisher:
Wiley
Publication Date:
2018
detail.hit.zdb_id:
2425880-5