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Patrick M. Lynch

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

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Helena A. Yu and Gregory J. Riely

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

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Wen-Zhuo He, Wan-Ming Hu, Fang Wang, Yu-Ming Rong, Lin Yang, Qian-Kun Xie, Yuan-Zhong Yang, Chang Jiang, Hui-Juan Qiu, Jia-Bin Lu, Bei Zhang, Pei-Rong Ding, Xiao-Jun Xia, Jian-Yong Shao, and Liang-Ping Xia

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

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Shilpa Grover and Sapna Syngal

). 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

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Ronald S. Go, Eric Jacobsen, Robert Baiocchi, Ilia Buhtoiarov, Erin B. Butler, Patrick K. Campbell, Don W. Coulter, Eli Diamond, Aron Flagg, Aaron M. Goodman, Gaurav Goyal, Dita Gratzinger, Paul C. Hendrie, Meghan Higman, Michael D. Hogarty, Filip Janku, Reem Karmali, David Morgan, Anne C. Raldow, Alexandra Stefanovic, Srinivas K. Tantravahi, Kelly Walkovich, Ling Zhang, Mary Anne Bergman, and Susan D. Darlow

-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

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Daniel G. Coit, John A. Thompson, Mark R. Albertini, Christopher Barker, William E. Carson III, Carlo Contreras, Gregory A. Daniels, Dominick DiMaio, Ryan C. Fields, Martin D. Fleming, Morganna Freeman, Anjela Galan, Brian Gastman, Valerie Guild, Douglas Johnson, Richard W. Joseph, Julie R. Lange, Sameer Nath, Anthony J. Olszanski, Patrick Ott, Aparna Priyanath Gupta, Merrick I. Ross, April K. Salama, Joseph Skitzki, Jeffrey Sosman, Susan M. Swetter, Kenneth K. Tanabe, Evan Wuthrick, Nicole R. McMillian, and Anita M. Engh

BRAF mutation status or PD-L1 expression status. Based on the demonstrated improvement in RFS, the FDA approved nivolumab for adjuvant treatment of resected nodal or metastatic melanoma ( Table 2 ). Although the trial entry criteria required patients

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Céline Mascaux, Ming-Sound Tsao, and Fred R. Hirsch

appropriate first-line therapy ( Table 1 ). Patients harboring an EGFR -sensitizing mutation, ALK or ROS1 rearrangements, or a BRAF mutation should receive an EGFR TKI (eg, gefitinib, erlotinib, afatinib), an ALK TKI (eg, crizotinib, ceritinib), a ROS1

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Paul F. Engstrom, Mara G. Bloom, George Daniel Demetri, Phillip G. Febbo, William Goeckeler, Marc Ladanyi, Bryan Loy, Kate Murphy, Michael Nerenberg, Paul Papagni, Mark Robson, Robert W. Sweetman, Sean Tunis, Jessica DeMartino, and Jonathan K. Larsen

( ER/PR ), and for the Onco type DX test (Genomic Health, Inc., Redwood City, CA). Other clinical guidelines include recommendations for KRAS mutation , BRAF mutation, and microsatellite instability testing. The increased use and complexity of some

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Margaret von Mehren, John M. Kane III, Richard F. Riedel, Jason K. Sicklick, Seth M. Pollack, Mark Agulnik, Marilyn M. Bui, Janai Carr-Ascher, Edwin Choy, Mary Connelly, Sarah Dry, Kristen N. Ganjoo, Ricardo J. Gonzalez, Ashley Holder, Jade Homsi, Vicki Keedy, Ciara M. Kelly, Edward Kim, David Liebner, Martin McCarter, Sean V. McGarry, Nathan W. Mesko, Christian Meyer, Alberto S. Pappo, Amanda M. Parkes, Ivy A. Petersen, Matthew Poppe, Scott Schuetze, Jacob Shabason, Matthew B. Spraker, Melissa Zimel, Mary Anne Bergman, Hema Sundar, and Lisa E. Hang

, Novel V600E BRAF mutations in imatinib-naive and imatinib-resistant gastrointestinal stromal tumors . Genes Chromosomes Cancer 2008 ; 47 : 853 – 859 . 10.1002/gcc.20589 18615679 44. Hostein I , Faur N , Primois C , BRAF mutation

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David S. Ettinger, Douglas E. Wood, Wallace Akerley, Lyudmila A. Bazhenova, Hossein Borghaei, David Ross Camidge, Richard T. Cheney, Lucian R. Chirieac, Thomas A. D’Amico, Todd L. Demmy, Thomas J. Dilling, M. Chris Dobelbower, Ramaswamy Govindan, Frederic W. Grannis Jr, Leora Horn, Thierry M. Jahan, Ritsuko Komaki, Lee M. Krug, Rudy P. Lackner, Michael Lanuti, Rogerio Lilenbaum, Jules Lin, Billy W. Loo Jr, Renato Martins, Gregory A. Otterson, Jyoti D. Patel, Katherine M. Pisters, Karen Reckamp, Gregory J. Riely, Eric Rohren, Steven E. Schild, Theresa A. Shapiro, Scott J. Swanson, Kurt Tauer, Stephen C. Yang, Kristina Gregory, and Miranda Hughes

ALK gene rearrangements are usually highly sensitive to ALK inhibitors. 4 , 5 , 8 – 10 Other actionable molecular abnormalities continue to be discovered and explored, including BRAF mutations and ROS1 and RET rearrangements. 7 , 21 – 25