;PMID: 9010458 ;source_file_1225.mrg ;Release 0.9 of PennBioIE ;Funded by NSF ITR EIA-0205448 ;0)section:[e:0..32] = [t:0..32] ;1)sentence:[e:37..155] = [t:37..155] ;2)section:[e:159..263] = [t:159..263] ;3)section:[e:267..386] = [t:267..386] ;4)sentence:[e:390..504] = [t:390..504] ;5)sentence:[e:505..573] = [t:505..573] ;6)sentence:[e:574..698] = [t:574..698] ;7)sentence:[e:700..817] = [t:700..817] ;8)sentence:[e:818..874] = [t:818..874] ;9)sentence:[e:875..987] = [t:875..987] ;10)sentence:[e:988..1322] = [t:988..1322] ;11)sentence:[e:1323..1462] = [t:1323..1462] ;12)sentence:[e:1463..1520] = [t:1463..1520] ;13)sentence:[e:1521..1602] = [t:1521..1602] ;14)sentence:[e:1603..1791] = [t:1603..1791] ;15)sentence:[e:1792..1938] = [t:1792..1938] ;16)sentence:[e:1939..2031] = [t:1939..2031] ;17)sentence:[e:2032..2338] = [t:2032..2338] ;18)sentence:[e:2339..2531] = [t:2339..2531] ;19)sentence:[e:2532..2796] = [t:2532..2796] ;20)section:[e:2800..2844] = [t:2800..2844] ;section 0 Span:0..32 ;Lab Invest 1997 Jan;76(1):153-9 (SEC (FRAG (RB:[0..3] Lab) (VB:[4..10] Invest) (CD:[12..16] 1997) (CC:[17..24] Jan;76-LRB-) (CD:[24..25] 1) (-RRB-:[25..26] -RRB-) (CD:[26..30] :153) (::[30..31] -) (CD:[31..32] 9))) ;sentence 1 Span:37..155 ;Sporadic and Thorotrast-induced angiosarcomas of the liver manifest frequent ;and multiple point mutations in K-ras-2. ;[37..45]:malignancy:"Sporadic" ;[50..68]:malignancy:"Thorotrast-induced" ;[69..95]:malignancy:"angiosarcomas of the liver" ;[128..143]:variation-type:"point mutations" ;[147..154]:gene-rna:"K-ras-2" (SENT (S-HLN (NP-SBJ (NP (ADJP (ADJP (JJ:[37..45] Sporadic)) (CC:[46..49] and) (ADJP (NN:[50..60] Thorotrast) (HYPH:[60..61] -) (VBN:[61..68] induced))) (NNS:[69..82] angiosarcomas)) (PP (IN:[83..85] of) (NP (DT:[86..89] the) (NN:[90..95] liver)))) (VP (VBP:[96..104] manifest) (NP (ADJP (JJ:[105..113] frequent) (CC:[114..117] and) (JJ:[119..127] multiple)) (NN:[128..133] point) (NNS:[134..143] mutations)) (PP-LOC (IN:[144..146] in) (NP (NN:[147..154] K-ras-2)))) (.:[154..155] .))) ;section 2 Span:159..263 ;Przygodzki RM, Finkelstein SD, Keohavong P, Zhu D, Bakker A, Swalsky PA, ;Soini Y, Ishak KG, Bennett WP. (SEC (FRAG (NNP:[159..169] Przygodzki) (NNP:[170..172] RM) (,:[172..173] ,) (NNP:[174..185] Finkelstein) (NNP:[186..188] SD) (,:[188..189] ,) (NNP:[190..199] Keohavong) (NNP:[200..201] P) (,:[201..202] ,) (NNP:[203..206] Zhu) (NNP:[207..208] D) (,:[208..209] ,) (NNP:[210..216] Bakker) (NNP:[217..218] A) (,:[218..219] ,) (NNP:[220..227] Swalsky) (NNP:[228..230] PA) (,:[230..231] ,) (NNP:[232..237] Soini) (NNP:[239..240] Y) (,:[240..241] ,) (NNP:[242..247] Ishak) (NNP:[248..250] KG) (,:[250..251] ,) (NNP:[252..259] Bennett) (NNP:[260..262] WP) (.:[262..263] .))) ;section 3 Span:267..386 ;Laboratory of Human Carcinogenesis, National Cancer Institute, National ;Institutes of Health, Bethesda, Maryland, USA. (SEC (FRAG (NNP:[267..277] Laboratory) (IN:[278..280] of) (NNP:[281..286] Human) (NNP:[287..301] Carcinogenesis) (,:[301..302] ,) (NNP:[303..311] National) (NNP:[312..318] Cancer) (NNP:[319..328] Institute) (,:[328..329] ,) (NNP:[330..338] National) (NNPS:[340..350] Institutes) (IN:[351..353] of) (NNP:[354..360] Health) (,:[360..361] ,) (NNP:[362..370] Bethesda) (,:[370..371] ,) (NNP:[372..380] Maryland) (,:[380..381] ,) (NNP:[382..385] USA) (.:[385..386] .))) ;sentence 4 Span:390..504 ;Hepatic angiosarcoma (HA) is an uncommon neoplasm associated with known ;etiologic factors in 25% to 42% of cases. ;[390..410]:malignancy:"Hepatic angiosarcoma" ;[412..414]:malignancy:"HA" ;[431..439]:malignancy:"neoplasm" (SENT (S (NP-SBJ (NP (JJ:[390..397] Hepatic) (NN:[398..410] angiosarcoma)) (NP (-LRB-:[411..412] -LRB-) (NN:[412..414] HA) (-RRB-:[414..415] -RRB-))) (VP (VBZ:[416..418] is) (NP-PRD (NP (DT:[419..421] an) (JJ:[422..430] uncommon) (NN:[431..439] neoplasm)) (VP (VBN:[440..450] associated) (NP (-NONE-:[450..450] *)) (PP-CLR (IN:[451..455] with) (NP (VBN:[456..461] known) (JJ:[463..472] etiologic) (NNS:[473..480] factors))) (PP (IN:[481..483] in) (NP (NP (QP (CD:[484..486] 25) (NN:[486..487] %) (TO:[488..490] to) (CD:[491..493] 42)) (NN:[493..494] %)) (PP (IN:[495..497] of) (NP (NNS:[498..503] cases)))))))) (.:[503..504] .))) ;sentence 5 Span:505..573 ;It is, however, one of the most common sarcomas found in the liver. ;[545..553]:malignancy:"sarcomas" (SENT (S (NP-SBJ (PRP:[505..507] It)) (VP (VBZ:[508..510] is) (,:[510..511] ,) (ADVP (RB:[512..519] however)) (,:[519..520] ,) (NP-PRD (NP (CD:[521..524] one)) (PP (IN:[525..527] of) (NP (NP (DT:[528..531] the) (ADJP (RBS:[532..536] most) (JJ:[537..543] common)) (NNS:[545..553] sarcomas)) (VP (VBN:[554..559] found) (NP (-NONE-:[559..559] *)) (PP-LOC (IN:[560..562] in) (NP (DT:[563..566] the) (NN:[567..572] liver)))))))) (.:[572..573] .))) ;sentence 6 Span:574..698 ;The aim of this study was to find was to find mutations in the K-ras-2 ;oncogene in sporadic and Thorotrast (TT)-induced HA. ;[638..645]:gene-rna:"K-ras-2" ;[658..666]:malignancy:"sporadic" ;[671..694]:malignancy:"Thorotrast (TT)-induced" ;[695..697]:malignancy:"HA" (SENT (S (NP-SBJ (NP (DT:[574..577] The) (NN:[578..581] aim)) (PP (IN:[582..584] of) (NP (DT:[585..589] this) (NN:[590..595] study)))) (X (VBD:[596..599] was) (TO:[600..602] to) (VB:[603..607] find)) (VP (VBD:[608..611] was) (S-PRD (NP-SBJ (-NONE-:[611..611] *)) (VP (TO:[612..614] to) (VP (VB:[615..619] find) (NP (NP (NNS:[621..630] mutations)) (PP-LOC (IN:[631..633] in) (NP (DT:[634..637] the) (NN:[638..645] K-ras-2) (NN:[646..654] oncogene)))) (PP (IN:[655..657] in) (NP (NP (JJ:[658..666] sporadic) (NML-1 (-NONE-:[666..666] *P*))) (CC:[667..670] and) (NP (ADJP (NML (NML (NN:[671..681] Thorotrast)) (NML (-LRB-:[682..683] -LRB-) (NN:[683..685] TT) (-RRB-:[685..686] -RRB-))) (HYPH:[686..687] -) (VBN:[687..694] induced)) (NML-1 (NN:[695..697] HA))))))))) (.:[697..698] .))) ;sentence 7 Span:700..817 ;Point mutations in K-ras-2 were sought in archival, formalin-fixed tissue ;blocks from 24 patients with angiosarcoma. ;[700..715]:variation-type:"Point mutations" ;[719..726]:gene-rna:"K-ras-2" ;[804..816]:malignancy:"angiosarcoma" (SENT (S (NP-SBJ-1 (NP (NN:[700..705] Point) (NNS:[706..715] mutations)) (PP-LOC (IN:[716..718] in) (NP (NN:[719..726] K-ras-2)))) (VP (VBD:[727..731] were) (VP (VBN:[732..738] sought) (NP-1 (-NONE-:[738..738] *)) (PP-LOC (IN:[739..741] in) (NP (NP (JJ:[742..750] archival) (,:[750..751] ,) (ADJP (NN:[752..760] formalin) (HYPH:[760..761] -) (VBN:[761..766] fixed)) (NN:[767..773] tissue) (NNS:[774..780] blocks)) (PP (IN:[782..786] from) (NP (NP (CD:[787..789] 24) (NNS:[790..798] patients)) (PP (IN:[799..803] with) (NP (NN:[804..816] angiosarcoma))))))))) (.:[816..817] .))) ;sentence 8 Span:818..874 ;Of these, 19 cases were sporadic and 5 were TT-induced. ;[842..850]:malignancy:"sporadic" ;[863..873]:malignancy:"TT-induced" (SENT (S (PP-1 (IN:[818..820] Of) (NP (DT:[821..826] these))) (,:[826..827] ,) (S (NP-SBJ (NP (CD:[828..830] 19) (NNS:[831..836] cases)) (PP-1 (-NONE-:[836..836] *T*))) (VP (VBD:[837..841] were) (ADJP-PRD (JJ:[842..850] sporadic)))) (CC:[851..854] and) (S (NP-SBJ (NP (CD:[855..856] 5)) (PP-1 (-NONE-:[856..856] *T*))) (VP (VBD:[857..861] were) (ADJP-PRD (NN:[863..865] TT) (HYPH:[865..866] -) (VBN:[866..873] induced)))) (.:[873..874] .))) ;sentence 9 Span:875..987 ;Mutational analysis was performed by topographic microdissection with PCR ;amplification followed by genotyping. (SENT (S (NP-SBJ-1 (JJ:[875..885] Mutational) (NN:[886..894] analysis)) (VP (VBD:[895..898] was) (VP (VBN:[899..908] performed) (NP-1 (-NONE-:[908..908] *)) (PP-MNR (IN:[909..911] by) (NP (NP (JJ:[912..923] topographic) (NN:[924..939] microdissection)) (PP (IN:[941..945] with) (NP (NP (NN:[946..949] PCR) (NN:[950..963] amplification)) (VP (VBN:[964..972] followed) (NP (-NONE-:[972..972] *)) (PP (IN:[973..975] by) (NP-LGS (NN:[976..986] genotyping)))))))))) (.:[986..987] .))) ;sentence 10 Span:988..1322 ;Specific mutations were determined by two independent methods: (a) direct ;sequencing of the PCR product confirmed by rePCR and by using a different ;sequencing primer, and (b) PCR-based selective enrichment of mutant DNA by ;endonuclease digestion followed by heteroduplex DNA analysis using ;denaturing gradient gel electrophoresis. ;[1214..1226]:gene-protein:"endonuclease" (SENT (S (NP-SBJ-1 (JJ:[988..996] Specific) (NNS:[997..1006] mutations)) (VP (VBD:[1007..1011] were) (VP (VBN:[1013..1023] determined) (NP-1 (-NONE-:[1023..1023] *)) (PP (IN:[1024..1026] by) (NP (NP (CD:[1027..1030] two) (JJ:[1031..1042] independent) (NNS:[1043..1050] methods)) (::[1050..1051] :) (NP (LST (LS:[1052..1055] -LRB-a-RRB-)) (NP (NP (NP (JJ:[1056..1062] direct) (NN:[1063..1073] sequencing)) (PP (IN:[1074..1076] of) (NP (DT:[1077..1080] the) (NN:[1081..1084] PCR) (NN:[1085..1092] product)))) (VP (VBN:[1094..1103] confirmed) (NP (-NONE-:[1103..1103] *)) (PP-MNR (PP (IN:[1104..1106] by) (NP (NN:[1107..1112] rePCR))) (CC:[1113..1116] and) (PP (IN:[1117..1119] by) (S (NP-SBJ (-NONE-:[1119..1119] *)) (VP (VBG:[1120..1125] using) (NP (DT:[1126..1127] a) (JJ:[1128..1137] different) (NN:[1138..1148] sequencing) (NN:[1149..1155] primer)))))))) (,:[1155..1156] ,) (CC:[1157..1160] and) (LST (LS:[1161..1164] -LRB-b-RRB-)) (NP (NP (NP (NP (ADJP (NN:[1165..1168] PCR) (HYPH:[1168..1169] -) (VBN:[1169..1174] based)) (JJ:[1176..1185] selective) (NN:[1186..1196] enrichment)) (PP (IN:[1197..1199] of) (NP (JJ:[1200..1206] mutant) (NN:[1207..1210] DNA))) (PP (IN:[1211..1213] by) (NP (NN:[1214..1226] endonuclease) (NN:[1227..1236] digestion)))) (VP (VBN:[1237..1245] followed) (NP (-NONE-:[1245..1245] *)) (PP (IN:[1246..1248] by) (NP-LGS (NN:[1250..1262] heteroduplex) (NN:[1263..1266] DNA) (NN:[1267..1275] analysis))))) (VP (VBG:[1276..1281] using) (NP (VBG:[1282..1292] denaturing) (NN:[1293..1301] gradient) (NN:[1302..1305] gel) (NN:[1306..1321] electrophoresis))))))))) (.:[1321..1322] .))) ;sentence 11 Span:1323..1462 ;Eleven K-ras-2 point mutations were detected in 7 of 24 (29%) tumors, ;including 5 of 19 (26%) sporadic HA and 2 of 5 (40%) TT-induced HA. ;[1331..1338]:gene-rna:"K-ras-2" ;[1339..1354]:variation-type:"point mutations" ;[1386..1392]:malignancy:"tumors" ;[1419..1430]:malignancy:"sporadic HA" ;[1448..1461]:malignancy:"TT-induced HA" (SENT (S (NP-SBJ-1 (CD:[1323..1329] Eleven) (NN:[1331..1338] K-ras-2) (NN:[1339..1344] point) (NNS:[1345..1354] mutations)) (VP (VBD:[1355..1359] were) (VP (VBN:[1360..1368] detected) (NP-1 (-NONE-:[1368..1368] *)) (PP (IN:[1369..1371] in) (NP (NP (CD:[1372..1373] 7)) (PP (IN:[1374..1376] of) (NP (NP (CD:[1377..1379] 24) (PRN (-LRB-:[1380..1381] -LRB-) (NP (CD:[1381..1383] 29) (NN:[1383..1384] %)) (-RRB-:[1384..1385] -RRB-)) (NNS:[1386..1392] tumors)) (,:[1392..1393] ,) (PP (VBG:[1394..1403] including) (NP (NP (NP (CD:[1404..1405] 5)) (PP (IN:[1406..1408] of) (NP (CD:[1409..1411] 19) (PRN (-LRB-:[1413..1414] -LRB-) (NP (CD:[1414..1416] 26) (NN:[1416..1417] %)) (-RRB-:[1417..1418] -RRB-)) (JJ:[1419..1427] sporadic) (NN:[1428..1430] HA)))) (CC:[1431..1434] and) (NP (NP (CD:[1435..1436] 2)) (PP (IN:[1437..1439] of) (NP (CD:[1440..1441] 5) (PRN (-LRB-:[1442..1443] -LRB-) (NP (CD:[1443..1445] 40) (NN:[1445..1446] %)) (-RRB-:[1446..1447] -RRB-)) (ADJP (NN:[1448..1450] TT) (HYPH:[1450..1451] -) (VBN:[1451..1458] induced)) (NN:[1459..1461] HA)))))))))))) (.:[1461..1462] .))) ;sentence 12 Span:1463..1520 ;There were seven G:C > A:T and four G:C > T:A mutations. ;[1480..1483]:variation-state-original:"G:C" ;[1486..1489]:variation-state-altered:"A:T" ;[1500..1503]:variation-state-original:"G:C" ;[1506..1509]:variation-state-altered:"T:A" ;[1510..1519]:variation-event:"mutations" (SENT (S (NP-SBJ (EX:[1463..1468] There)) (VP (VBD:[1469..1473] were) (NP-PRD (NP (CD:[1474..1479] seven) (NML (NN:[1480..1483] G:C) (PP (SYM:[1484..1485] >) (NP (NN:[1486..1489] A:T)))) (NML-1 (-NONE-:[1489..1489] *P*))) (CC:[1490..1493] and) (NP (CD:[1495..1499] four) (NML (NML (NN:[1500..1503] G:C)) (PP (SYM:[1504..1505] >) (NP (NN:[1506..1509] T:A)))) (NML-1 (NNS:[1510..1519] mutations))))) (.:[1519..1520] .))) ;sentence 13 Span:1521..1602 ;All seven mutated tumors contained a codon 12-aspartate amino acid ;substitution. ;[1539..1545]:malignancy:"tumors" ;[1558..1567]:variation-location:"codon 12" ;[1568..1577]:variation-state-altered:"aspartate" ;[1578..1601]:variation-type:"amino acid substitution" (SENT (S (NP-SBJ (DT:[1521..1524] All) (CD:[1525..1530] seven) (VBN:[1531..1538] mutated) (NNS:[1539..1545] tumors)) (VP (VBD:[1546..1555] contained) (NP (DT:[1556..1557] a) (NML (NML (NN:[1558..1563] codon) (CD:[1565..1567] 12)) (HYPH:[1567..1568] -) (NML (NN:[1568..1577] aspartate))) (NML (JJ:[1578..1583] amino) (NN:[1584..1588] acid)) (NN:[1589..1601] substitution))) (.:[1601..1602] .))) ;sentence 14 Span:1603..1791 ;In addition, a second codon 12-cysteine mutant cell population was present ;in one of two codon 12-aspartate mutated TT-induced HA and in three of five ;codon 12-aspartate sporadic tumors. ;[1625..1633]:variation-location:"codon 12" ;[1634..1642]:variation-state-altered:"cysteine" ;[1693..1701]:variation-location:"codon 12" ;[1702..1711]:variation-state-altered:"aspartate" ;[1721..1734]:malignancy:"TT-induced HA" ;[1756..1764]:variation-location:"codon 12" ;[1765..1774]:variation-state-altered:"aspartate" ;[1775..1790]:malignancy:"sporadic tumors" (SENT (S (PP (IN:[1603..1605] In) (NP (NN:[1606..1614] addition))) (,:[1614..1615] ,) (NP-SBJ (DT:[1616..1617] a) (JJ:[1618..1624] second) (NML (NML (NN:[1625..1630] codon) (CD:[1631..1633] 12)) (HYPH:[1633..1634] -) (NN:[1634..1642] cysteine)) (JJ:[1644..1650] mutant) (NN:[1651..1655] cell) (NN:[1656..1666] population)) (VP (VBD:[1667..1670] was) (ADJP-PRD (JJ:[1671..1678] present)) (PP-LOC (PP (IN:[1679..1681] in) (NP (NP (CD:[1682..1685] one)) (PP (IN:[1686..1688] of) (NP (CD:[1689..1692] two) (ADJP (NML (NML (NN:[1693..1698] codon) (CD:[1699..1701] 12)) (HYPH:[1701..1702] -) (NN:[1702..1711] aspartate)) (VBN:[1712..1719] mutated)) (ADJP (NN:[1721..1723] TT) (HYPH:[1723..1724] -) (VBN:[1724..1731] induced)) (NN:[1732..1734] HA))))) (CC:[1735..1738] and) (PP (IN:[1739..1741] in) (NP (NP (CD:[1742..1747] three)) (PP (IN:[1748..1750] of) (NP (CD:[1751..1755] five) (NML (NML (NN:[1756..1761] codon) (CD:[1762..1764] 12)) (HYPH:[1764..1765] -) (NN:[1765..1774] aspartate)) (JJ:[1775..1783] sporadic) (NNS:[1784..1790] tumors))))))) (.:[1790..1791] .))) ;sentence 15 Span:1792..1938 ;Of these four tumors, three contained both aspartate and cysteine mutations ;and were composed of multiple nodules; the fourth was a single mass. ;[1807..1813]:malignancy:"tumors" ;[1836..1845]:variation-state-altered:"aspartate" ;[1850..1858]:variation-state-altered:"cysteine" ;[1859..1868]:variation-event:"mutations" (SENT (S (PP-1 (IN:[1792..1794] Of) (NP (DT:[1795..1800] these) (CD:[1802..1806] four) (NNS:[1807..1813] tumors))) (,:[1813..1814] ,) (S (NP-SBJ-3 (NP (CD:[1815..1820] three)) (PP-1 (-NONE-:[1820..1820] *T*))) (VP (VP (VBD:[1821..1830] contained) (NP (CC:[1831..1835] both) (NP (NN:[1836..1845] aspartate) (NML-2 (-NONE-:[1845..1845] *P*))) (CC:[1846..1849] and) (NP (NN:[1850..1858] cysteine) (NML-2 (NNS:[1859..1868] mutations))))) (CC:[1869..1872] and) (VP (VBD:[1873..1877] were) (VP (VBN:[1879..1887] composed) (NP-3 (-NONE-:[1887..1887] *)) (PP-CLR (IN:[1888..1890] of) (NP (JJ:[1891..1899] multiple) (NNS:[1900..1907] nodules))))))) (::[1907..1908] ;) (S (NP-SBJ (NP (DT:[1909..1912] the) (JJ:[1913..1919] fourth)) (PP-1 (-NONE-:[1919..1919] *T*))) (VP (VBD:[1920..1923] was) (NP-PRD (DT:[1924..1925] a) (JJ:[1926..1932] single) (NN:[1933..1937] mass)))) (.:[1937..1938] .))) ;sentence 16 Span:1939..2031 ;Seventeen tumors had multiple nodules; whereas 5 had a K-ras-2 mutation, 12 ;were wild-type. ;[1949..1955]:malignancy:"tumors" ;[1995..2002]:gene-rna:"K-ras-2" ;[2003..2011]:variation-event:"mutation" (SENT (S (NP-SBJ (CD:[1939..1948] Seventeen) (NNS:[1949..1955] tumors)) (VP (VBD:[1956..1959] had) (NP (JJ:[1961..1969] multiple) (NNS:[1970..1977] nodules)) (::[1977..1978] ;) (SBAR-ADV (IN:[1979..1986] whereas) (S (S (NP-SBJ (CD:[1987..1988] 5)) (VP (VBD:[1989..1992] had) (NP (DT:[1993..1994] a) (NN:[1995..2002] K-ras-2) (NN:[2003..2011] mutation)))) (,:[2011..2012] ,) (S (NP-SBJ (CD:[2013..2015] 12)) (VP (VBD:[2016..2020] were) (NP-PRD (JJ:[2021..2025] wild) (HYPH:[2025..2026] -) (NN:[2026..2030] type))))))) (.:[2030..2031] .))) ;sentence 17 Span:2032..2338 ;The molecular pathology of both sporadic and TT-induced HA is characterized ;by a high rate of K-ras-2 mutations characteristic of oxidative damage (ie, ;G:C > A:T and G:C > T:A mutations) resulting in two mutated population sets: ;codon 12 GGT > GAT and GGT > TGT (glycine to aspartic acid and cysteine). ;[2065..2073]:malignancy:"sporadic" ;[2078..2088]:malignancy:"TT-induced" ;[2089..2091]:malignancy:"HA" ;[2128..2135]:gene-rna:"K-ras-2" ;[2136..2145]:variation-event:"mutations" ;[2186..2189]:variation-state-original:"G:C" ;[2192..2195]:variation-state-altered:"A:T" ;[2201..2204]:variation-state-original:"G:C" ;[2207..2210]:variation-state-altered:"T:A" ;[2211..2220]:variation-event:"mutations" ;[2264..2272]:variation-location:"codon 12" ;[2273..2276]:variation-state-original:"GGT" ;[2280..2283]:variation-state-altered:"GAT" ;[2288..2291]:variation-state-original:"GGT" ;[2294..2297]:variation-state-altered:"TGT" ;[2299..2306]:variation-state-original:"glycine" ;[2310..2323]:variation-state-altered:"aspartic acid" ;[2328..2336]:variation-state-altered:"cysteine" (SENT (S (NP-SBJ-2 (NP (DT:[2032..2035] The) (JJ:[2037..2046] molecular) (NN:[2047..2056] pathology)) (PP (IN:[2057..2059] of) (NP (CC:[2060..2064] both) (NP (JJ:[2065..2073] sporadic) (NML-1 (-NONE-:[2073..2073] *P*))) (CC:[2074..2077] and) (NP (ADJP (NN:[2078..2080] TT) (HYPH:[2080..2081] -) (VBN:[2081..2088] induced)) (NML-1 (NN:[2089..2091] HA)))))) (VP (VBZ:[2092..2094] is) (VP (VBN:[2095..2108] characterized) (NP-2 (-NONE-:[2108..2108] *)) (PP (IN:[2109..2111] by) (NP-LGS (NP (NP (NP (DT:[2112..2113] a) (JJ:[2115..2119] high) (NN:[2120..2124] rate)) (PP (IN:[2125..2127] of) (NP (NN:[2128..2135] K-ras-2) (NNS:[2136..2145] mutations)))) (ADJP (JJ:[2146..2160] characteristic) (PP (IN:[2161..2163] of) (NP (JJ:[2164..2173] oxidative) (NN:[2174..2180] damage)))) (PRN (-LRB-:[2181..2182] -LRB-) (NP (ADVP (FW:[2182..2184] ie)) (,:[2184..2185] ,) (NP (NP (NML (NML (NN:[2186..2189] G:C)) (PP (SYM:[2190..2191] >) (NP (NN:[2192..2195] A:T)))) (NML-3 (-NONE-:[2195..2195] *P*))) (CC:[2197..2200] and) (NP (NML (NML (NN:[2201..2204] G:C)) (PP (SYM:[2205..2206] >) (NP (NN:[2207..2210] T:A)))) (NML-3 (NNS:[2211..2220] mutations))))) (-RRB-:[2220..2221] -RRB-))) (VP (VBG:[2222..2231] resulting) (PP-CLR (IN:[2232..2234] in) (NP (NP (CD:[2235..2238] two) (VBN:[2239..2246] mutated) (NN:[2247..2257] population) (NNS:[2258..2262] sets)) (::[2262..2263] :) (NP (NP (NML-4 (NN:[2264..2269] codon) (CD:[2270..2272] 12)) (NML (NML (NN:[2273..2276] GGT)) (PP (SYM:[2278..2279] >) (NP (NN:[2280..2283] GAT))))) (CC:[2284..2287] and) (NP (NML-4 (-NONE-:[2287..2287] *P*)) (NML (NML (NN:[2288..2291] GGT)) (PP (SYM:[2292..2293] >) (NP (NN:[2294..2297] TGT)))) (PRN (-LRB-:[2298..2299] -LRB-) (NP (NP (NN:[2299..2306] glycine)) (PP (TO:[2307..2309] to) (NP (NP (JJ:[2310..2318] aspartic) (NN:[2319..2323] acid)) (CC:[2324..2327] and) (NP (NN:[2328..2336] cysteine))))) (-RRB-:[2336..2337] -RRB-))))))))))) (.:[2337..2338] .))) ;sentence 18 Span:2339..2531 ;This is, to date, the first study to characterize the K-ras-2 gene mutations ;within human sporadic and TT-induced HA by direct sequence analysis and ;denaturing gradient gel electrophoresis. ;[2394..2401]:gene-rna:"K-ras-2" ;[2430..2438]:malignancy:"sporadic" ;[2444..2454]:malignancy:"TT-induced" ;[2455..2457]:malignancy:"HA" (SENT (S (NP-SBJ (DT:[2339..2343] This)) (VP (VBZ:[2344..2346] is) (,:[2346..2347] ,) (PP-TMP (TO:[2348..2350] to) (NP (NN:[2351..2355] date))) (,:[2355..2356] ,) (NP-PRD (NP (DT:[2358..2361] the) (JJ:[2362..2367] first) (NN:[2368..2373] study)) (S (NP-SBJ (-NONE-:[2373..2373] *)) (VP (TO:[2374..2376] to) (VP (VB:[2377..2389] characterize) (NP (NP (DT:[2390..2393] the) (NN:[2394..2401] K-ras-2) (NN:[2402..2406] gene) (NNS:[2407..2416] mutations)) (PP (IN:[2417..2423] within) (NP (NP (JJ:[2424..2429] human) (JJ:[2430..2438] sporadic) (NML-1 (-NONE-:[2438..2438] *P*))) (CC:[2440..2443] and) (NP (ADJP (NN:[2444..2446] TT) (HYPH:[2446..2447] -) (VBN:[2447..2454] induced)) (NML-1 (NN:[2455..2457] HA)))))) (PP-MNR (IN:[2458..2460] by) (NP (NP (JJ:[2461..2467] direct) (NN:[2468..2476] sequence) (NN:[2477..2485] analysis)) (CC:[2486..2489] and) (NP (VBG:[2490..2500] denaturing) (NN:[2501..2509] gradient) (NN:[2510..2513] gel) (NN:[2515..2530] electrophoresis))))))))) (.:[2530..2531] .))) ;sentence 19 Span:2532..2796 ;These data further support the hypothesis linking adduct-forming vinyl ;chloride exposure to HA containing a much higher frequency of K-ras-2 ;mutations and a mutational spectrum characteristic of chloroethylene oxide, ;a carcinogenic metabolite of vinyl chloride. ;[2625..2627]:malignancy:"HA" ;[2667..2674]:gene-rna:"K-ras-2" (SENT (S (NP-SBJ (DT:[2532..2537] These) (NNS:[2538..2542] data)) (ADVP (RBR:[2543..2550] further)) (VP (VBP:[2551..2558] support) (NP (NP (DT:[2559..2562] the) (NN:[2563..2573] hypothesis)) (VP (VBG:[2574..2581] linking) (NP (NP (ADJP (NN:[2583..2589] adduct) (HYPH:[2589..2590] -) (VBG:[2590..2597] forming)) (NN:[2598..2603] vinyl) (NN:[2604..2612] chloride) (NN:[2613..2621] exposure)) (PP (TO:[2622..2624] to) (NP (NP (NP (NN:[2625..2627] HA)) (VP (VBG:[2628..2638] containing) (NP (NP (DT:[2639..2640] a) (ADJP (RB:[2641..2645] much) (JJR:[2646..2652] higher)) (NN:[2653..2662] frequency)) (PP (IN:[2664..2666] of) (NP (NN:[2667..2674] K-ras-2) (NNS:[2675..2684] mutations)))))) (CC:[2685..2688] and) (NP (NP (DT:[2689..2690] a) (JJ:[2691..2701] mutational) (NN:[2702..2710] spectrum)) (ADJP (JJ:[2711..2725] characteristic) (PP (IN:[2726..2728] of) (NP (NP (NN:[2729..2743] chloroethylene) (NN:[2745..2750] oxide)) (,:[2750..2751] ,) (NP (NP (DT:[2752..2753] a) (JJ:[2754..2766] carcinogenic) (NN:[2767..2777] metabolite)) (PP (IN:[2778..2780] of) (NP (NN:[2781..2786] vinyl) (NN:[2787..2795] chloride)))))))))))))) (.:[2795..2796] .))) ;section 20 Span:2800..2844 ;PMID: 9010458 [PubMed - indexed for MEDLINE] (SEC (FRAG (NNP:[2800..2804] PMID) (::[2804..2805] :) (CD:[2806..2813] 9010458) (NN:[2814..2815] -LSB-) (NNP:[2815..2821] PubMed) (::[2822..2823] -) (NN:[2824..2831] indexed) (IN:[2832..2835] for) (NNP:[2836..2844] MEDLINE-RSB-)))