;PMID: 9816185 ;source_file_1385.mrg ;Release 0.9 of PennBioIE ;Funded by NSF ITR EIA-0205448 ;0)section:[e:0..36] = [t:0..36] ;1)sentence:[e:41..116] = [t:41..116] ;2)section:[e:120..202] = [t:120..202] ;3)section:[e:206..322] = [t:206..322] ;4)sentence:[e:326..419] = [t:326..419] ;5)sentence:[e:420..759] = [t:420..759] ;6)sentence:[e:760..806] = [t:760..806] ;7)sentence:[e:807..957] = [t:807..957] ;8)sentence:[e:959..1129] = [t:959..1129] ;9)sentence:[e:1130..1234] = [t:1130..1234] ;10)sentence:[e:1235..1360] = [t:1235..1360] ;11)sentence:[e:1362..1550] = [t:1362..1550] ;12)sentence:[e:1551..1780] = [t:1551..1780] ;13)sentence:[e:1781..1936] = [t:1781..1936] ;14)sentence:[e:1937..2157] = [t:1937..2157] ;15)section:[e:2161..2205] = [t:2161..2205] ;section 0 Span:0..36 ;Clin Cancer Res 1996 Feb;2(2):411-8 (SEC (FRAG (NNP:[0..4] Clin) (NN:[5..11] Cancer) (NNP:[12..15] Res) (CD:[17..21] 1996) (-LRB-:[22..28] Feb;2-LRB-) (CD:[28..29] 2) (-RRB-:[29..30] -RRB-) (CD:[30..34] :411) (::[34..35] -) (CD:[35..36] 8))) ;sentence 1 Span:41..116 ;Detection of K-ras mutations in lung carcinomas: relationship to prognosis. ;[54..59]:gene-rna:"K-ras" ;[73..88]:malignancy:"lung carcinomas" (SENT (NP-HLN (NP (NP (NN:[41..50] Detection)) (PP (IN:[51..53] of) (NP (NN:[54..59] K-ras) (NNS:[60..69] mutations))) (PP-LOC (IN:[70..72] in) (NP (NN:[73..77] lung) (NNS:[78..88] carcinomas)))) (::[88..89] :) (NP (NP (NN:[90..102] relationship)) (PP (TO:[103..105] to) (NP (NN:[106..115] prognosis)))) (.:[115..116] .))) ;section 2 Span:120..202 ;Keohavong P, DeMichele MA, Melacrinos AC, Landreneau RJ, Weyant RJ, Siegfried ; JM. (SEC (FRAG (NNP:[120..129] Keohavong) (NNP:[130..131] P) (,:[131..132] ,) (NNP:[133..142] DeMichele) (NNP:[143..145] MA) (,:[145..146] ,) (NNP:[147..157] Melacrinos) (NNP:[158..160] AC) (,:[160..161] ,) (NNP:[162..172] Landreneau) (NNP:[173..175] RJ) (,:[175..176] ,) (NNP:[177..183] Weyant) (NNP:[184..186] RJ) (,:[186..187] ,) (NNP:[188..197] Siegfried) (NNP:[199..201] JM) (.:[201..202] .))) ;section 3 Span:206..322 ;Department of Environmental and Occupational Health, University of ;Pittsburgh, Pittsburgh, Pennsylvania 15238, USA. (SEC (FRAG (NN:[206..216] Department) (IN:[217..219] of) (NNP:[220..233] Environmental) (CC:[234..237] and) (NNP:[238..250] Occupational) (NNP:[251..257] Health) (,:[257..258] ,) (NNP:[259..269] University) (IN:[270..272] of) (NNP:[273..283] Pittsburgh) (,:[283..284] ,) (NNP:[286..296] Pittsburgh) (,:[296..297] ,) (NNP:[298..310] Pennsylvania) (NNP:[311..316] 15238) (,:[316..317] ,) (NNP:[318..321] USA) (.:[321..322] .))) ;sentence 4 Span:326..419 ;The K-ras mutation is one of the most common genetic alterations found in ;human lung cancer. ;[330..335]:gene-rna:"K-ras" ;[407..418]:malignancy:"lung cancer" (SENT (S (NP-SBJ (DT:[326..329] The) (NN:[330..335] K-ras) (NN:[336..344] mutation)) (VP (VBZ:[345..347] is) (NP-PRD (NP (CD:[348..351] one)) (PP (IN:[352..354] of) (NP (NP (DT:[355..358] the) (ADJP (RBS:[359..363] most) (JJ:[364..370] common)) (JJ:[371..378] genetic) (NNS:[379..390] alterations)) (VP (VBN:[391..396] found) (NP (-NONE-:[396..396] *)) (PP (IN:[397..399] in) (NP (JJ:[400..405] human) (NN:[407..411] lung) (NN:[412..418] cancer)))))))) (.:[418..419] .))) ;sentence 5 Span:420..759 ;To evaluate the prognostic value of ras gene alterations in lung cancer in a ;U.S. population, we have screened 173 human lung tumors, which included 127 ;adenocarcinomas, 37 squamous carcinomas, and 9 adenosquamous carcinomas, for ;mutations in the K-ras gene using the combination of the PCR and denaturing ;gradient gel electrophoresis. ;[456..459]:gene-rna:"ras" ;[480..492]:malignancy:"lung cancer" ;[542..553]:malignancy:"lung tumors" ;[575..590]:malignancy:"adenocarcinomas" ;[595..614]:malignancy:"squamous carcinomas" ;[622..647]:malignancy:"adenosquamous carcinomas" ;[670..675]:gene-rna:"K-ras" (SENT (S (S-PRP (NP-SBJ (-NONE-:[420..420] *)) (VP (TO:[420..422] To) (VP (VB:[423..431] evaluate) (NP (NP (DT:[432..435] the) (JJ:[436..446] prognostic) (NN:[447..452] value)) (PP (IN:[453..455] of) (NP (NN:[456..459] ras) (NN:[460..464] gene) (NNS:[465..476] alterations))) (PP (IN:[477..479] in) (NP (NN:[480..484] lung) (NN:[486..492] cancer)))) (PP (IN:[493..495] in) (NP (DT:[496..497] a) (NNP:[498..502] U.S.) (NN:[503..513] population)))))) (,:[513..514] ,) (NP-SBJ (PRP:[515..517] we)) (VP (VBP:[518..522] have) (VP (VBN:[523..531] screened) (NP (NP (CD:[532..535] 173) (JJ:[536..541] human) (NN:[542..546] lung) (NNS:[547..553] tumors)) (,:[553..554] ,) (SBAR (WHNP-1 (WDT:[555..560] which)) (S (NP-SBJ-1 (-NONE-:[560..560] *T*)) (VP (VBD:[562..570] included) (NP (NP (CD:[571..574] 127) (NNS:[575..590] adenocarcinomas)) (,:[590..591] ,) (NP (CD:[592..594] 37) (JJ:[595..603] squamous) (NNS:[604..614] carcinomas)) (,:[614..615] ,) (CC:[616..619] and) (NP (CD:[620..621] 9) (JJ:[622..635] adenosquamous) (NNS:[637..647] carcinomas))))))) (,:[647..648] ,) (PP (IN:[649..652] for) (NP (NP (NNS:[653..662] mutations)) (PP-LOC (IN:[663..665] in) (NP (DT:[666..669] the) (NN:[670..675] K-ras) (NN:[676..680] gene))))) (S-MNR (NP-SBJ (-NONE-:[680..680] *)) (VP (VBG:[681..686] using) (NP (NP (DT:[687..690] the) (NN:[691..702] combination)) (PP (IN:[703..705] of) (NP (NP (DT:[706..709] the) (NN:[710..713] PCR)) (CC:[714..717] and) (NP (VBG:[719..729] denaturing) (NN:[730..738] gradient) (NN:[739..742] gel) (NN:[743..758] electrophoresis))))))))) (.:[758..759] .))) ;sentence 6 Span:760..806 ;Forty-three tumors contained K-ras mutations. ;[772..778]:malignancy:"tumors" ;[789..794]:gene-rna:"K-ras" (SENT (S (NP-SBJ (CD:[760..771] Forty-three) (NNS:[772..778] tumors)) (VP (VBD:[779..788] contained) (NP (NN:[789..794] K-ras) (NNS:[796..805] mutations))) (.:[805..806] .))) ;sentence 7 Span:807..957 ;Of these, 41 were identified among the adenocarcinomas (32%), 1 among the ;squamous carcinomas (2.7%), and 1 among the adenosquamous carcinomas (11%). ;[846..861]:malignancy:"adenocarcinomas" ;[882..901]:malignancy:"squamous carcinomas" ;[926..950]:malignancy:"adenosquamous carcinomas" (SENT (S (S (PP (IN:[807..809] Of) (NP (DT:[810..815] these))) (,:[815..816] ,) (NP-SBJ-3=1 (CD:[817..819] 41)) (VP (VBD:[820..824] were) (VP (VBN:[825..835] identified) (NP-3 (-NONE-:[835..835] *)) (PP=2 (IN:[836..841] among) (NP (DT:[842..845] the) (NNS:[846..861] adenocarcinomas) (PRN (-LRB-:[862..863] -LRB-) (NP (CD:[863..865] 32) (NN:[865..866] %)) (-RRB-:[866..867] -RRB-))))))) (,:[867..868] ,) (S (NP-SBJ=1 (CD:[869..870] 1)) (PP=2 (IN:[871..876] among) (NP (DT:[878..881] the) (JJ:[882..890] squamous) (NNS:[891..901] carcinomas) (PRN (-LRB-:[902..903] -LRB-) (NP (CD:[903..906] 2.7) (NN:[906..907] %)) (-RRB-:[907..908] -RRB-))))) (,:[908..909] ,) (CC:[910..913] and) (S (NP-SBJ=1 (CD:[914..915] 1)) (PP=2 (IN:[916..921] among) (NP (DT:[922..925] the) (JJ:[926..939] adenosquamous) (NNS:[940..950] carcinomas) (PRN (-LRB-:[951..952] -LRB-) (NP (CD:[952..954] 11) (NN:[954..955] %)) (-RRB-:[955..956] -RRB-))))) (.:[956..957] .))) ;sentence 8 Span:959..1129 ;Forty of these mutations were found in codon 12 and consisted of 24 G to T ;transversions, 12 G to A transitions, 2 G to C transversions, and 1 double GG ;to TT mutation. ;[998..1006]:variation-location:"codon 12" ;[1027..1028]:variation-state-original:"G" ;[1032..1033]:variation-state-altered:"T" ;[1035..1048]:variation-type:"transversions" ;[1053..1054]:variation-state-original:"G" ;[1058..1059]:variation-state-altered:"A" ;[1060..1071]:variation-type:"transitions" ;[1075..1076]:variation-state-original:"G" ;[1080..1081]:variation-state-altered:"C" ;[1082..1095]:variation-type:"transversions" ;[1110..1112]:variation-state-original:"GG" ;[1117..1119]:variation-state-altered:"TT" ;[1120..1128]:variation-event:"mutation" (SENT (S (NP-SBJ-1 (NP (CD:[959..964] Forty)) (PP (IN:[965..967] of) (NP (DT:[968..973] these) (NNS:[974..983] mutations)))) (VP (VP (VBD:[984..988] were) (VP (VBN:[989..994] found) (NP-1 (-NONE-:[994..994] *)) (PP-LOC (IN:[995..997] in) (NP (NN:[998..1003] codon) (CD:[1004..1006] 12))))) (CC:[1007..1010] and) (VP (VBD:[1011..1020] consisted) (PP-CLR (IN:[1021..1023] of) (NP (NP (CD:[1024..1026] 24) (NML (NML (NN:[1027..1028] G)) (PP (TO:[1029..1031] to) (NP (NN:[1032..1033] T)))) (NNS:[1035..1048] transversions)) (,:[1048..1049] ,) (NP (CD:[1050..1052] 12) (NML (NML (NN:[1053..1054] G)) (PP (TO:[1055..1057] to) (NP (NN:[1058..1059] A)))) (NNS:[1060..1071] transitions)) (,:[1071..1072] ,) (NP (CD:[1073..1074] 2) (NML (NML (NN:[1075..1076] G)) (PP (TO:[1077..1079] to) (NP (NN:[1080..1081] C)))) (NNS:[1082..1095] transversions)) (,:[1095..1096] ,) (CC:[1097..1100] and) (NP (CD:[1101..1102] 1) (NML (NML (JJ:[1103..1109] double) (NN:[1110..1112] GG)) (PP (TO:[1113..1115] to) (NP (NN:[1117..1119] TT)))) (NN:[1120..1128] mutation)))))) (.:[1128..1129] .))) ;sentence 9 Span:1130..1234 ;Two other G to T transversions were found in codon 13, and 1 A to C ;transversion was found in codon 61. ;[1140..1141]:variation-state-original:"G" ;[1145..1146]:variation-state-altered:"T" ;[1147..1160]:variation-type:"transversions" ;[1175..1183]:variation-location:"codon 13" ;[1191..1192]:variation-state-original:"A" ;[1196..1197]:variation-state-altered:"C" ;[1199..1211]:variation-type:"transversion" ;[1225..1233]:variation-location:"codon 61" (SENT (S (S (NP-SBJ-2 (CD:[1130..1133] Two) (JJ:[1134..1139] other) (NML (NML (NN:[1140..1141] G)) (PP (TO:[1142..1144] to) (NP (NN:[1145..1146] T)))) (NNS:[1147..1160] transversions)) (VP (VBD:[1161..1165] were) (VP (VBN:[1166..1171] found) (NP-2 (-NONE-:[1171..1171] *)) (PP-LOC (IN:[1172..1174] in) (NP (NN:[1175..1180] codon) (CD:[1181..1183] 13)))))) (,:[1183..1184] ,) (CC:[1185..1188] and) (S (NP-SBJ-1 (CD:[1189..1190] 1) (NML (NML (NN:[1191..1192] A)) (PP (TO:[1193..1195] to) (NP (NN:[1196..1197] C)))) (NN:[1199..1211] transversion)) (VP (VBD:[1212..1215] was) (VP (VBN:[1216..1221] found) (NP-1 (-NONE-:[1221..1221] *)) (PP-LOC (IN:[1222..1224] in) (NP (NN:[1225..1230] codon) (CD:[1231..1233] 61)))))) (.:[1233..1234] .))) ;sentence 10 Span:1235..1360 ;The data showed that gender did not seem to affect the incidence and the ;types of the K-ras mutations or amino acid changes. ;[1322..1327]:gene-rna:"K-ras" (SENT (S (NP-SBJ (DT:[1235..1238] The) (NNS:[1239..1243] data)) (VP (VBD:[1244..1250] showed) (SBAR (IN:[1251..1255] that) (S (NP-SBJ-1 (NN:[1256..1262] gender)) (VP (VBD:[1263..1266] did) (RB:[1267..1270] not) (VP (VB:[1271..1275] seem) (S (NP-SBJ-1 (-NONE-:[1275..1275] *)) (VP (TO:[1276..1278] to) (VP (VB:[1280..1286] affect) (NP (NP (NP (DT:[1287..1290] the) (NN:[1291..1300] incidence)) (CC:[1301..1304] and) (NP (DT:[1305..1308] the) (NNS:[1309..1314] types))) (PP (IN:[1315..1317] of) (NP (NP (DT:[1318..1321] the) (NN:[1322..1327] K-ras) (NNS:[1328..1337] mutations)) (CC:[1338..1340] or) (NP (JJ:[1341..1346] amino) (NN:[1347..1351] acid) (NNS:[1352..1359] changes))))))))))))) (.:[1359..1360] .))) ;sentence 11 Span:1362..1550 ;Examination of the mutations in adenocarcinomas in relation to overall ;survival showed no difference in adenocarcinomas with K-ras mutations ;compared with K-ras-negative adenocarcinomas. ;[1394..1409]:malignancy:"adenocarcinomas" ;[1467..1482]:malignancy:"adenocarcinomas" ;[1488..1493]:gene-rna:"K-ras" ;[1519..1524]:gene-rna:"K-ras" ;[1534..1549]:malignancy:"adenocarcinomas" (SENT (S (NP-SBJ (NP (NN:[1362..1373] Examination)) (PP (IN:[1374..1376] of) (NP (NP (DT:[1377..1380] the) (NNS:[1381..1390] mutations)) (PP (IN:[1391..1393] in) (NP (NNS:[1394..1409] adenocarcinomas))))) (PP (IN:[1410..1412] in) (NP (NP (NN:[1413..1421] relation)) (PP (TO:[1422..1424] to) (NP (JJ:[1425..1432] overall) (NN:[1433..1441] survival)))))) (VP (VBD:[1443..1449] showed) (NP (DT:[1450..1452] no) (NN:[1453..1463] difference)) (PP (IN:[1464..1466] in) (NP (NP (NP (NNS:[1467..1482] adenocarcinomas)) (PP (IN:[1483..1487] with) (NP (NN:[1488..1493] K-ras) (NNS:[1494..1503] mutations)))) (VP (VBN:[1504..1512] compared) (NP (-NONE-:[1512..1512] *)) (PP-CLR (IN:[1513..1517] with) (NP (ADJP (NN:[1519..1524] K-ras) (HYPH:[1524..1525] -) (JJ:[1525..1533] negative)) (NNS:[1534..1549] adenocarcinomas))))))) (.:[1549..1550] .))) ;sentence 12 Span:1551..1780 ;However, the substitution of the wild-type GGT (glycine) at codon 12 with a ;GTT (valine) or a CGT (arginine) showed a strong trend (P = 0.07) toward a ;poorer prognosis compared with wild-type or other amino acid substitutions. ;[1564..1576]:variation-type:"substitution" ;[1594..1597]:variation-state-original:"GGT" ;[1600..1607]:variation-state-original:"glycine" ;[1612..1620]:variation-location:"codon 12" ;[1628..1631]:variation-state-altered:"GTT" ;[1633..1639]:variation-state-altered:"valine" ;[1646..1649]:variation-state-altered:"CGT" ;[1651..1659]:variation-state-altered:"arginine" ;[1755..1779]:variation-type:"amino acid substitutions" (SENT (S (ADVP (RB:[1551..1558] However)) (,:[1558..1559] ,) (NP-SBJ (NP (DT:[1560..1563] the) (NN:[1564..1576] substitution)) (PP (IN:[1577..1579] of) (NP (DT:[1580..1583] the) (NML (JJ:[1584..1588] wild) (HYPH:[1588..1589] -) (NN:[1589..1593] type)) (NN:[1594..1597] GGT) (PRN (-LRB-:[1599..1600] -LRB-) (NP (NN:[1600..1607] glycine)) (-RRB-:[1607..1608] -RRB-)))) (PP-LOC (IN:[1609..1611] at) (NP (NN:[1612..1617] codon) (CD:[1618..1620] 12))) (PP (IN:[1621..1625] with) (NP (NP (DT:[1626..1627] a) (NN:[1628..1631] GTT) (PRN (-LRB-:[1632..1633] -LRB-) (NP (NN:[1633..1639] valine)) (-RRB-:[1639..1640] -RRB-))) (CC:[1641..1643] or) (NP (DT:[1644..1645] a) (NN:[1646..1649] CGT) (PRN (-LRB-:[1650..1651] -LRB-) (NP (NN:[1651..1659] arginine)) (-RRB-:[1659..1660] -RRB-)))))) (VP (VBD:[1661..1667] showed) (NP (NP (DT:[1668..1669] a) (JJ:[1670..1676] strong) (NN:[1678..1683] trend) (PRN (-LRB-:[1684..1685] -LRB-) (S (NP-SBJ (NN:[1685..1686] P)) (VP (SYM:[1687..1688] =) (NP (CD:[1689..1693] 0.07)))) (-RRB-:[1693..1694] -RRB-))) (PP (IN:[1695..1701] toward) (NP (DT:[1702..1703] a) (JJR:[1704..1710] poorer) (NN:[1711..1720] prognosis)))) (VP (VBN:[1721..1729] compared) (NP (-NONE-:[1729..1729] *)) (PP-CLR (IN:[1730..1734] with) (NP (NP (NML (JJ:[1735..1739] wild) (HYPH:[1739..1740] -) (NN:[1740..1744] type)) (NML-1 (-NONE-:[1744..1744] *P*))) (CC:[1745..1747] or) (NP (JJ:[1748..1753] other) (NML-1 (JJ:[1755..1760] amino) (NN:[1761..1765] acid) (NNS:[1766..1779] substitutions))))))) (.:[1779..1780] .))) ;sentence 13 Span:1781..1936 ;Substitution of the wild-type glycine for aspartate (GAT) showed a strong ;trend (P = 0.06) for a better outcome than the valine or arginine ;substitution. ;[1781..1793]:variation-type:"Substitution" ;[1811..1818]:variation-state-original:"glycine" ;[1823..1832]:variation-state-altered:"aspartate" ;[1835..1838]:variation-state-altered:"GAT" ;[1903..1909]:variation-state-altered:"valine" ;[1914..1922]:variation-state-altered:"arginine" ;[1923..1935]:variation-type:"substitution" (SENT (S (NP-SBJ (NP (NN:[1781..1793] Substitution)) (PP (IN:[1794..1796] of) (NP (DT:[1797..1800] the) (NML (JJ:[1801..1805] wild) (HYPH:[1805..1806] -) (NN:[1806..1810] type)) (NN:[1811..1818] glycine))) (PP (IN:[1819..1822] for) (NP (NN:[1823..1832] aspartate) (PRN (-LRB-:[1834..1835] -LRB-) (NP (NN:[1835..1838] GAT)) (-RRB-:[1838..1839] -RRB-))))) (VP (VBD:[1840..1846] showed) (NP (DT:[1847..1848] a) (JJ:[1849..1855] strong) (NN:[1856..1861] trend) (PRN (-LRB-:[1862..1863] -LRB-) (S (NP-SBJ (NN:[1863..1864] P)) (VP (SYM:[1865..1866] =) (NP (CD:[1867..1871] 0.06)))) (-RRB-:[1871..1872] -RRB-))) (PP (IN:[1873..1876] for) (NP (NP (DT:[1877..1878] a) (JJR:[1879..1885] better) (NN:[1886..1893] outcome)) (PP (IN:[1894..1898] than) (NP (DT:[1899..1902] the) (NML (NML (NN:[1903..1909] valine) (NML-1 (-NONE-:[1909..1909] *P*))) (CC:[1910..1912] or) (NML (NN:[1914..1922] arginine) (NML-1 (NN:[1923..1935] substitution))))))))) (.:[1935..1936] .))) ;sentence 14 Span:1937..2157 ;Although these trends will require larger patient populations for ;verification, these data suggest that the prognostic significance of K-ras ;mutations may depend on the amino acid substitution in the p21(ras) ;protein. ;[2074..2079]:gene-rna:"K-ras" ;[2108..2131]:variation-type:"amino acid substitution" ;[2140..2148]:gene-protein:"p21(ras)" (SENT (S (SBAR-ADV (IN:[1937..1945] Although) (S (NP-SBJ (DT:[1946..1951] these) (NNS:[1952..1958] trends)) (VP (MD:[1959..1963] will) (VP (VB:[1964..1971] require) (NP (JJR:[1972..1978] larger) (NN:[1979..1986] patient) (NNS:[1988..1999] populations)) (PP (IN:[2000..2003] for) (NP (NN:[2004..2016] verification))))))) (,:[2016..2017] ,) (NP-SBJ (DT:[2018..2023] these) (NNS:[2024..2028] data)) (VP (VBP:[2029..2036] suggest) (SBAR (IN:[2037..2041] that) (S (NP-SBJ (NP (DT:[2042..2045] the) (JJ:[2046..2056] prognostic) (NN:[2058..2070] significance)) (PP (IN:[2071..2073] of) (NP (NN:[2074..2079] K-ras) (NNS:[2080..2089] mutations)))) (VP (MD:[2090..2093] may) (VP (VB:[2094..2100] depend) (PP-CLR (IN:[2101..2103] on) (NP (NP (DT:[2104..2107] the) (NML (JJ:[2108..2113] amino) (NN:[2114..2118] acid)) (NN:[2119..2131] substitution)) (PP-LOC (IN:[2132..2134] in) (NP (DT:[2135..2138] the) (NN:[2140..2148] p21-LRB-ras-RRB-) (NN:[2149..2156] protein)))))))))) (.:[2156..2157] .))) ;section 15 Span:2161..2205 ;PMID: 9816185 [PubMed - indexed for MEDLINE] (SEC (FRAG (NNP:[2161..2165] PMID) (::[2165..2166] :) (CD:[2167..2174] 9816185) (IN:[2175..2176] -LSB-) (NNP:[2176..2182] PubMed) (HYPH:[2183..2184] -) (JJ:[2185..2192] indexed) (IN:[2193..2196] for) (NNP:[2197..2205] MEDLINE-RSB-)))