非表示:
キーワード:
metastatic melanoma, primary melanoma, BRAFV600 mutation, BRAF inhibitor
要旨:
Background: The detection of BRAFV600 mutations in patients with metastatic
melanoma is important because of the availability of BRAF inhibitor therapy. However,
the clinical relevance of the frequency of BRAFV600 mutant alleles is unclear.
Patients and Methods: Allele frequencies of BRAFV600 mutations were analyzed
byultra-deepnext-generation sequencing in formalin-fixed, paraffin-embedded
melanoma tissue (75 primary melanomas and 88 matched metastases). In a second
study, pretreatment specimens from 76 patients who received BRAF inhibitors were
retrospectively analyzed, and BRAFV600 allele frequencies were correlated with
therapeutic results.
Results: Thirty-five patients had concordantly BRAF-positive and 36 (48%)
patients had concordantly BRAF-negative primary melanomas and matched
metastases, and four patients had discordant samples with low allele frequencies
(3.4–5.2%). Twenty-six of 35 patients with concordant samples had BRAFV600E
mutations, three of whom had additional mutations (V600K in two patients and
V600R in one) and nine patients had exclusively non-V600E mutations (V600K in eight
patients and V600E -c.1799_1800TG > AA- in one patient). The frequency of mutated
BRAFV600 alleles was similar in the primary melanoma and matched metastasis
in 27/35 patients, but differed by >3-fold in 8/35 of samples. BRAFV600E allele
frequencies in pretreatment tumor specimens were not significantly correlated with
treatment outcomes in 76 patients with metastatic melanoma who were treated with
BRAF inhibitors.
Conclusions: BRAFV600 mutation status and allele frequency is consistent in
the majority of primary melanomas and matched metastases. A small subgroup of
patients has double mutations. BRAFV600 allele frequencies are not correlated with
the response to BRAF inhibitors.