BACKGROUND: The detection of BRAFV600 mutations in @entity1 with @entity320 is important because of the availability of @entity817 inhibitor therapy. However, the clinical relevance of the frequency of BRAFV600 mutant alleles is unclear. @entity1 AND METHODS: Allele frequencies of BRAFV600 mutations were analyzed by ultra-deep next generation sequencing in @entity406 -fixed, @entity982 -embedded @entity320 tissue (75 primary @entity320 and 88 matched @entity3 ). In a second study, pretreatment specimens from 76 @entity1 who received @entity817 inhibitors were retrospectively analyzed, and BRAFV600 allele frequencies were correlated with therapeutic results. RESULTS: Thirty-five @entity1 had concordantly @entity817 -positive and 36 (48%) @entity1 had concordantly @entity817 -negative primary @entity320 and matched @entity3 , and four @entity1 had discordant samples with low allele frequencies (3.4-5.2%). Twenty-six of 35 @entity1 with concordant samples had BRAFV600E mutations, three of whom had additional mutations ( @entity16232 in two @entity1 and @entity17330 in one) and nine @entity1 had exclusively non- @entity8554 mutations ( @entity16232 in eight @entity1 and @entity8554 - @entity69942 - in one @entity1 ). The frequency of mutated BRAFV600 alleles was similar in the primary @entity320 and matched metastasis in 27/35 @entity1 , but differed by >3-fold in 8/35 of samples. BRAFV600E allele frequencies in @entity5 specimens were not significantly correlated with treatment outcomes in 76 @entity1 with @entity320 who were treated with @entity817 inhibitors. CONCLUSIONS: BRAFV600 mutation status and allele frequency is consistent in the majority of primary @entity320 and matched @entity3 . A small subgroup of @entity1 has double mutations. BRAFV600 allele frequencies are not correlated with the response to @entity817 inhibitors.

Allele frequencies of BRAFV600 mutations in primary @entity320 and matched XXXX and their relevance for @entity817 inhibitor therapy in @entity320 .

@entity1 :: ('9606', 'Species') :: ['patients', 'patient', 'PATIENTS'] @entity17330 :: ('p|SUB|V|600|R', 'ProteinMutation') :: ['V600R'] @entity69942 :: ('c|SUB|TG|1799_1800|AA', 'DNAMutation') :: ['c.1799_1800TG > AA'] @entity5 :: ('MESH:D009369', 'Disease') :: ['pretreatment tumor'] @entity406 :: ('MESH:D005557', 'Chemical') :: ['formalin'] @entity16232 :: ('p|SUB|V|600|K', 'ProteinMutation') :: ['V600K'] @entity982 :: ('MESH:D010232', 'Chemical') :: ['paraffin'] @entity8554 :: ('p|SUB|V|600|E', 'ProteinMutation') :: ['V600E'] @entity3 :: ('MESH:D009362', 'Disease') :: ['metastases'] @entity817 :: ('673', 'Gene') :: ['BRAF'] @entity320 :: ('MESH:D008545', 'Disease') :: ['melanoma', 'melanomas', 'metastatic melanoma']
@entity3 :: (MESH:D009362,Disease) :: ['metastases']
