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T1 Age 2 13 44-year-old T2 Personal_background 14 21 Chinese T3 Sex 22 25 man T4 History 33 60 7 pack-year smoking history T5 Clinical_event 65 73 referred E1 Clinical_event:T5 T6 Nonbiological_location 77 104 Shanghai Pulmonary Hospital R1 MODIFY Arg1:T6 Arg2:E1 T7 Date 108 121 February 2013 E2 Date:T7 T8 Sign_symptom 149 153 mass E3 Sign_symptom:T8 T9 Biological_structure 144 148 lung T10 Biological_structure 128 143 left upper lobe R2 MODIFY Arg1:T9 Arg2:E3 R3 MODIFY Arg1:T10 Arg2:E3 T11 Sign_symptom 193 203 metastases E4 Sign_symptom:T11 T12 Biological_structure 178 192 intrapulmonary T13 Detailed_description 168 177 bilateral T14 Detailed_description 159 167 multiple R4 MODIFY Arg1:T12 Arg2:E4 R5 MODIFY Arg1:T13 Arg2:E4 R6 MODIFY Arg1:T14 Arg2:E4 T15 Disease_disorder 210 226 pleural effusion E5 Disease_disorder:T15 T16 Detailed_description 205 209 left R7 MODIFY Arg1:T16 Arg2:E5 T17 Disease_disorder 246 261 lymphadenopathy E6 Disease_disorder:T17 T18 Lab_value 232 245 2R/4R/10L/11L R8 MODIFY Arg1:T18 Arg2:E6 T19 Diagnostic_procedure 277 285 cytology E7 Diagnostic_procedure:T19 T20 Biological_structure 263 276 Pleural fluid R9 MODIFY Arg1:T20 Arg2:E7 T21 Disease_disorder 295 309 adenocarcinoma E8 Disease_disorder:T21 T22 Diagnostic_procedure 314 363 Scorpion Amplification Refractory Mutation system E9 Diagnostic_procedure:T22 T23 Detailed_description 365 390 AmoyDx Co., Xiamen, China R10 MODIFY Arg1:T23 Arg2:E9 T24 Sign_symptom 414 455 epidermal growth factor receptor mutation E10 Sign_symptom:T24 A1 POLARITY E10 NEG T25 Medication 470 482 chemotherapy E11 Medication:T25 T26 Medication 488 499 gemcitabine E12 Medication:T26 T27 Medication 504 513 cisplatin E13 Medication:T27 R11 SUB_PROCEDURE Arg1:E12 Arg2:E11 R12 SUB_PROCEDURE Arg1:E13 Arg2:E11 T28 Sign_symptom 550 558 symptoms E14 Sign_symptom:T28 A2 TREND E14 INC T29 Disease_disorder 602 609 disease E15 Disease_disorder:T29 T30 Detailed_description 590 601 progressive R13 MODIFY Arg1:T30 Arg2:E15 T31 Clinical_event 613 641 second opinion was requested E16 Clinical_event:T31 T32 Nonbiological_location 651 673 University of Colorado R14 MODIFY Arg1:T32 Arg2:E16 T33 Diagnostic_procedure 707 713 biopsy E17 Diagnostic_procedure:T33 T34 Detailed_description 680 706 computed tomography–guided R15 MODIFY Arg1:T34 Arg2:E17 T35 Sign_symptom 737 743 lesion E18 Sign_symptom:T35 R16 MODIFY Arg1:E10 Arg2:E9 T36 Biological_structure 721 736 left upper lobe R17 MODIFY Arg1:T36 Arg2:E18 R18 MODIFY Arg1:E18 Arg2:E17 T37 Medication 836 846 pemetrexed E19 Medication:T37 T38 Medication 851 861 nedaplatin E20 Medication:T38 T39 Sign_symptom 899 918 shortness of breath E21 Sign_symptom:T39 A3 TREND E21 INC T40 Diagnostic_procedure 973 978 scans E22 Diagnostic_procedure:T40 T41 Sign_symptom 946 965 further progression E23 Sign_symptom:T41 R19 MODIFY Arg1:E23 Arg2:E22 T42 Diagnostic_procedure 1021 1027 biopsy E24 Diagnostic_procedure:T42 T43 Diagnostic_procedure 1081 1092 PCR testing E25 Diagnostic_procedure:T43 T44 Detailed_description 1062 1080 SNaPshot multiplex R20 MODIFY Arg1:T44 Arg2:E25 T45 Sign_symptom 1049 1058 mutations E26 Sign_symptom:T45 A4 POLARITY E26 NEG R21 MODIFY Arg1:E26 Arg2:E25 T46 Diagnostic_procedure 1188 1197 FISH test E27 Diagnostic_procedure:T46 T47 Detailed_description 1172 1187 ALK break-apart R22 MODIFY Arg1:T47 Arg2:E27 T48 Lab_value 1208 1233 atypical negative pattern R23 MODIFY Arg1:T48 Arg2:E27 T49 Diagnostic_procedure 1433 1450 diagnostic assays E28 Diagnostic_procedure:T49 T50 Medication 1738 1748 crizotinib E29 Medication:T50 T51 Dosage 1750 1768 250 mg twice daily R24 MODIFY Arg1:T51 Arg2:E29 T52 Date 1795 1803 May 2013 E30 Date:T52 T53 Sign_symptom 1823 1846 symptomatic improvement E31 Sign_symptom:T53 T54 Medication 1927 1937 crizotinib E32 Medication:T54 T55 Sign_symptom 1958 1969 progression E33 Sign_symptom:T55 A5 POLARITY E33 NEG T56 Date 1976 1990 September 2013 E34 Date:T56 T57 Lab_value 1249 1309 68% of cells demonstrated single copies of the 5′ ALK signal R25 MODIFY Arg1:T57 Arg2:E27 T58 Lab_value 1314 1395 numerous cells with doublets of the 5′ ALK signal combined with one 3′ ALK signal R26 MODIFY Arg1:T58 Arg2:E27 T59 Lab_value 1464 1486 ALK protein expression R27 MODIFY Arg1:T59 Arg2:E28 T60 Diagnostic_procedure 1490 1493 IHC E35 Diagnostic_procedure:T60 #1 AnnotatorNotes E35 immunohistochemistry T61 Detailed_description 1504 1517 D5F3 antibody R28 MODIFY Arg1:T61 Arg2:E35 R29 SUB_PROCEDURE Arg1:E35 Arg2:E28 T62 Detailed_description 1519 1562 Cell Signaling Technology Inc., Danvers, MA R30 MODIFY Arg1:T62 Arg2:T61 T63 Lab_value 1595 1680 presence of an echinoderm microtubule-associated protein-like 4 (EML4)-ALK transcript R31 MODIFY Arg1:T63 Arg2:E28 T64 Diagnostic_procedure 1695 1701 RT-PCR E36 Diagnostic_procedure:T64 R32 SUB_PROCEDURE Arg1:E36 Arg2:E28 * OVERLAP E1 E2 E3 E4 E5 E6 E7 E8 E9 E10 E11 R33 BEFORE Arg1:E11 Arg2:E14 * OVERLAP E14 E15 R34 BEFORE Arg1:E15 Arg2:E16 * OVERLAP E16 E17 E18 E19 E20 R35 BEFORE Arg1:E20 Arg2:E21 * OVERLAP E21 E23 E24 E26 E25 E27 E28 R36 BEFORE Arg1:E28 Arg2:E29 * OVERLAP E29 E30 R37 BEFORE Arg1:E30 Arg2:E31 T65 Date 1863 1876 after 1 month E37 Date:T65 * OVERLAP E31 E37 R38 BEFORE Arg1:E37 Arg2:E32 * OVERLAP E32 E33 E34 T66 Activity 45 52 smoking E38 Activity:T66 R39 BEFORE Arg1:E38 Arg2:E1