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molecularly selective settings. The targeting of the RAS/RAF/MEK/ERK pathway with clinically available surrogate markers harboring KRAS and/or BRAF mutations could be a strategy for selecting more responsive personalized cancer therapy using molecular

KIT gene are the most common, accounting for 80% to 85% of GIST mutations, with PDGFR α mutations representing 5% to 10% of mutations. The remaining mutations have been termed wild-type ; however, SDH and BRAF mutations have been identified

/kg + nivolumab 1 mg/kg for patients with bulky disease, liver metastases, and/or brain metastases. 1 Those with BRAF mutations who are hospitalized or receiving high doses of opioids may be administered BRAF/MEK inhibitors followed by immunotherapy. “For

from epigenetic hypermethylation of the hMLH1 promoter, and also typically showing BRAF mutation) are worth detecting because of differences in prognosis and response to adjuvant therapies that include 5-FU. 14 This is the position of the EGAPP. 15

hypermethylation, whereas absence of the BRAF mutation suggests a germline mutation in MLH1, and thus LS. Depending on the population and study design, the percentage of carcinomas that show loss of DNA MMR protein expression is approximately 15% (and reported

cases, an assay directed at detecting MLH-1 hypermethylation or its surrogate, BRAF mutation, may suggest the non-HNPCC/LS basis and a recommendation for no further HNPCC/LS-related testing. MSI/IHC testing is now often routine and does not require

and acquired BRAF mutations as potential mechanisms of resistance, both of which have potential therapeutic implications that will require further study. 23 , 24 Second-Generation EGFR TKIs Acquired resistance to first-generation EGFR TKIs

TS , . Mismatch repair status and BRAF mutation status in metastatic colorectal cancer patients: a pooled analysis of the CAIRO, CAIRO2, COIN, and FOCUS studies . Clin Cancer Res 2014 ; 20 : 5322 – 5330 . 25139339 10.1158/1078-0432.CCR-14-0332 17

). 33 Therefore, in tumors that show loss of MLH1 staining on IHC, it may be reasonable to perform BRAF mutation analysis for the p.V600E mutation associated with sporadic MLH1 promoter methylation before performing germline testing. Germline

-LCH is frequent in patients with pituitary, skin, and base-of-skull bone involvement. A study of children and young adults with LCH (n=1,897) showed that a BRAF mutation was present in 93.7% of patients with ND-LCH, compared with 54.1% in patients