;PMID: 9107428 ;source_file_1308.mrg ;Release 0.9 of PennBioIE ;Funded by NSF ITR EIA-0205448 ;0)section:[e:0..54] = [t:0..54] ;1)sentence:[e:59..108] = [t:59..108] ;2)section:[e:112..207] = [t:112..207] ;3)section:[e:211..307] = [t:211..307] ;4)sentence:[e:311..552] = [t:311..552] ;5)sentence:[e:554..673] = [t:554..673] ;6)sentence:[e:674..916] = [t:674..916] ;7)sentence:[e:917..1039] = [t:917..1039] ;8)sentence:[e:1040..1230] = [t:1040..1230] ;9)sentence:[e:1231..1386] = [t:1231..1386] ;10)sentence:[e:1387..1555] = [t:1387..1555] ;11)sentence:[e:1557..1629] = [t:1557..1629] ;12)sentence:[e:1630..1738] = [t:1630..1738] ;13)sentence:[e:1739..1887] = [t:1739..1887] ;14)section:[e:1891..1935] = [t:1891..1935] ;section 0 Span:0..54 ;Cancer Epidemiol Biomarkers Prev 1997 Apr;6(4):239-43 (SEC (FRAG (NNP:[0..6] Cancer) (NNP:[7..16] Epidemiol) (NNP:[17..27] Biomarkers) (NNP:[28..32] Prev) (CD:[34..38] 1997) (CC:[39..43] Apr;) (CD:[43..44] 6) (NN:[44..45] -LRB-) (NN:[45..46] 4) (NN:[46..47] -RRB-) (::[47..48] :) (CD:[48..51] 239) (CD:[51..54] -43))) ;sentence 1 Span:59..108 ;Ras oncogene mutations in childhood brain tumors. ;[59..62]:gene-rna:"Ras" ;[85..94]:malignancy-developmental-state:"childhood" ;[95..107]:malignancy-type:"brain tumors" (SENT (NP-HLN (NP (NN:[59..62] Ras) (NN:[63..71] oncogene) (NNS:[72..81] mutations)) (PP-LOC (IN:[82..84] in) (NP (NN:[85..94] childhood) (NN:[95..100] brain) (NNS:[101..107] tumors))) (.:[107..108] .))) ;section 2 Span:112..207 ;Maltzman TH, Mueller BA, Schroeder J, Rutledge JC, Patterson K, ;Preston-Martin S, Faustman EM. (SEC (FRAG (NNP:[112..120] Maltzman) (NNP:[121..123] TH) (,:[123..124] ,) (NNP:[125..132] Mueller) (NNP:[133..135] BA) (,:[135..136] ,) (NNP:[137..146] Schroeder) (NNP:[147..149] J,) (NNP:[150..158] Rutledge) (NNP:[159..161] JC) (,:[161..162] ,) (NNP:[163..172] Patterson) (NNP:[173..175] K,) (NNP:[176..183] Preston) (NNP:[183..190] -Martin) (NNP:[192..193] S) (,:[193..194] ,) (NNP:[195..203] Faustman) (NN:[204..206] EM) (.:[206..207] .))) ;section 3 Span:211..307 ;Division of Gastroenterology, University of Colorado Health Sciences Center, ;Denver 80262, USA. (SEC (FRAG (NNP:[211..219] Division) (IN:[220..222] of) (NNP:[223..239] Gastroenterology) (,:[239..240] ,) (NNP:[241..251] University) (IN:[252..254] of) (NNP:[255..263] Colorado) (NNP:[264..270] Health) (NNP:[271..279] Sciences) (NNP:[280..286] Center) (,:[286..287] ,) (NNP:[289..295] Denver) (CD:[296..301] 80262) (,:[301..302] ,) (NNP:[303..306] USA) (.:[306..307] .))) ;sentence 4 Span:311..552 ;Although N-nitroso compounds (NNC) are ubiquitous in the human environment ;and are known neurocarcinogens in animal models, results of epidemiological ;studies have not yet convincingly associated NNCs with brain tumor ;occurrence in humans. ;[519..530]:malignancy-type:"brain tumor" (SENT (S (SBAR-ADV (IN:[311..319] Although) (S (NP-SBJ (NP (NN:[320..329] N-nitroso) (NNS:[330..339] compounds)) (NP (-LRB-:[340..341] -LRB-) (NN:[341..344] NNC) (-RRB-:[344..345] -RRB-))) (VP (VP (VBP:[346..349] are) (ADJP-PRD (JJ:[350..360] ubiquitous)) (PP-LOC (IN:[361..363] in) (NP (DT:[364..367] the) (JJ:[368..373] human) (NN:[374..385] environment)))) (CC:[386..389] and) (VP (VBP:[391..394] are) (NP-LOC (VBN:[395..400] known) (NNS:[401..417] neurocarcinogens)) (PP (IN:[418..420] in) (NP (NN:[421..427] animal) (NNS:[428..434] models))))))) (,:[434..435] ,) (NP-SBJ (NP (NNS:[436..443] results)) (PP (IN:[444..446] of) (NP (JJ:[447..462] epidemiological) (NNS:[463..470] studies)))) (VP (VBP:[472..476] have) (RB:[477..480] not) (ADVP-TMP (RB:[481..484] yet)) (ADVP (RB:[485..497] convincingly)) (VP (VBN:[498..508] associated) (NP (NNS:[509..513] NNCs)) (PP-CLR (IN:[514..518] with) (NP (NP (NN:[519..524] brain) (NN:[525..530] tumor) (NN:[531..541] occurrence)) (PP (IN:[542..544] in) (NP (NNS:[545..551] humans))))))) (.:[551..552] .))) ;sentence 5 Span:554..673 ;Animal studies have suggested that specific codons (12, 13, and 61) in the ;ras family are mutable by exposure to NNCs. ;[598..604]...[618..620]:variation-location:"codons"..."61" ;[598..604]...[610..612]:variation-location:"codons"..."13" ;[598..604]...[606..608]:variation-location:"codons"..."12" ;[629..632]:gene-rna:"ras" (SENT (S (NP-SBJ (NN:[554..560] Animal) (NNS:[561..568] studies)) (VP (VBP:[569..573] have) (VP (VBN:[574..583] suggested) (SBAR (IN:[584..588] that) (S (NP-SBJ (NP (JJ:[589..597] specific) (NNS:[598..604] codons) (PRN (-LRB-:[605..606] -LRB-) (NP (NP (CD:[606..608] 12)) (,:[608..609] ,) (NP (CD:[610..612] 13)) (,:[612..613] ,) (CC:[614..617] and) (NP (CD:[618..620] 61))) (-RRB-:[620..621] -RRB-))) (PP (IN:[622..624] in) (NP (DT:[625..628] the) (NN:[629..632] ras) (NN:[634..640] family)))) (VP (VBP:[641..644] are) (ADJP-PRD (JJ:[645..652] mutable) (PP (IN:[653..655] by) (NP (NP (NN:[656..664] exposure)) (PP (TO:[665..667] to) (NP (NNS:[668..672] NNCs))))))))))) (.:[672..673] .))) ;sentence 6 Span:674..916 ;The purpose of this study was to measure the presence of mutations in the ;ras family of oncogenes in tissue from childhood brain (CB) tumors as a ;preliminary step toward investigating their potential use as biomarkers of ;chemical exposure. ;[749..752]:gene-rna:"ras" ;[789..798]:malignancy-developmental-state:"childhood" ;[799..816]:malignancy-type:"brain (CB) tumors" ;[806..808]:malignancy-type:"CB" (SENT (S (NP-SBJ (NP (DT:[674..677] The) (NN:[678..685] purpose)) (PP (IN:[686..688] of) (NP (DT:[689..693] this) (NN:[694..699] study)))) (VP (VBD:[700..703] was) (S-PRD (NP-SBJ (-NONE-:[703..703] *)) (VP (TO:[704..706] to) (VP (VB:[707..714] measure) (NP (NP (DT:[716..719] the) (NN:[720..728] presence)) (PP (IN:[729..731] of) (NP (NP (NNS:[732..741] mutations)) (PP (IN:[742..744] in) (NP (NP (DT:[745..748] the) (NN:[749..752] ras) (NN:[753..759] family)) (PP (IN:[760..762] of) (NP (NNS:[763..772] oncogenes)))))))) (PP-LOC (IN:[773..775] in) (NP (NP (NN:[776..782] tissue)) (PP (IN:[783..787] from) (NP (NML (NML (NN:[789..798] childhood) (NN:[799..804] brain)) (NML (-LRB-:[805..806] -LRB-) (NN:[806..808] CB) (-RRB-:[808..809] -RRB-))) (NNS:[810..816] tumors))))) (PP (IN:[817..819] as) (NP (NP (DT:[820..821] a) (JJ:[822..833] preliminary) (NN:[834..838] step)) (PP (IN:[839..845] toward) (S-NOM (NP-SBJ (-NONE-:[845..845] *)) (VP (VBG:[846..859] investigating) (NP (NP (PRP$:[860..865] their) (JJ:[867..876] potential) (NN:[877..880] use)) (PP (IN:[881..883] as) (NP (NP (NNS:[884..894] biomarkers)) (PP (IN:[895..897] of) (NP (JJ:[898..906] chemical) (NN:[907..915] exposure))))))))))))))) (.:[915..916] .))) ;sentence 7 Span:917..1039 ;DNA was extracted from paraffin-embedded formalin-fixed CB tumors from ;tissues resected during neurosurgical operations. ;[974..983]:malignancy-type:"CB tumors" (SENT (S (NP-SBJ-1 (NN:[917..920] DNA)) (VP (VBD:[921..924] was) (VP (VBN:[925..934] extracted) (NP-1 (-NONE-:[934..934] *)) (PP-CLR (IN:[935..939] from) (NP (NP (ADJP (NN:[941..949] paraffin) (HYPH:[949..950] -) (VBN:[950..958] embedded)) (ADJP (NN:[959..967] formalin) (HYPH:[967..968] -) (VBN:[968..973] fixed)) (NN:[974..976] CB) (NNS:[977..983] tumors)) (PP (IN:[984..988] from) (NP (NP (NNS:[989..996] tissues)) (VP (VBN:[997..1005] resected) (NP (-NONE-:[1005..1005] *)) (PP-TMP (IN:[1006..1012] during) (NP (JJ:[1014..1027] neurosurgical) (NNS:[1028..1038] operations)))))))))) (.:[1038..1039] .))) ;sentence 8 Span:1040..1230 ;Using the PCR, designed RFLP-screening methods, and sequencing, we attempted ;to screen brain tumors from 46 children for the presence of H, K, and N-ras ;mutations at codons 12, 13, and 61. ;[1128..1140]:malignancy-type:"brain tumors" ;[1149..1157]:malignancy-developmental-state:"children" ;[1179..1180]...[1191..1194]:gene-rna:"H"..."ras" ;[1182..1183]...[1191..1194]:gene-rna:"K"..."ras" ;[1189..1194]:gene-rna:"N-ras" ;[1195..1204]:variation-event:"mutations" ;[1208..1217]:variation-location:"codons 12" ;[1208..1214]...[1227..1229]:variation-location:"codons"..."61" ;[1208..1214]...[1219..1221]:variation-location:"codons"..."13" (SENT (S (S-MNR (NP-SBJ (-NONE-:[1040..1040] *)) (VP (VBG:[1040..1045] Using) (NP (NP (DT:[1046..1049] the) (NN:[1050..1053] PCR)) (,:[1053..1054] ,) (NP (VBN:[1055..1063] designed) (ADJP (NN:[1064..1068] RFLP) (HYPH:[1068..1069] -) (VBG:[1069..1078] screening)) (NNS:[1079..1086] methods)) (,:[1086..1087] ,) (CC:[1088..1091] and) (NP (NN:[1093..1103] sequencing))))) (,:[1103..1104] ,) (NP-SBJ (PRP:[1105..1107] we)) (VP (VBD:[1108..1117] attempted) (S (NP-SBJ (-NONE-:[1117..1117] *)) (VP (TO:[1118..1120] to) (VP (VB:[1121..1127] screen) (NP (NP (NN:[1128..1133] brain) (NNS:[1134..1140] tumors)) (PP (IN:[1141..1145] from) (NP (CD:[1146..1148] 46) (NNS:[1149..1157] children)))) (PP (IN:[1158..1161] for) (NP (NP (DT:[1162..1165] the) (NN:[1167..1175] presence)) (PP (IN:[1176..1178] of) (NP (NP (NP (NML (NN:[1179..1180] H) (NML-2 (-NONE-:[1180..1180] *P*))) (NML-1 (-NONE-:[1180..1180] *P*))) (,:[1180..1181] ,) (NP (NML (NN:[1182..1183] K) (NML-2 (-NONE-:[1183..1183] *P*))) (NML-1 (-NONE-:[1183..1183] *P*))) (,:[1183..1184] ,) (CC:[1185..1188] and) (NP (NML (NN:[1189..1190] N) (HYPH:[1190..1191] -) (NML-2 (NN:[1191..1194] ras))) (NML-1 (NNS:[1195..1204] mutations)))) (PP-LOC (IN:[1205..1207] at) (NP (NP (NML-3 (NNS:[1208..1214] codons)) (CD:[1215..1217] 12)) (,:[1217..1218] ,) (NP (NML-3 (-NONE-:[1218..1218] *P*)) (CD:[1219..1221] 13)) (,:[1221..1222] ,) (CC:[1223..1226] and) (NP (NML-3 (-NONE-:[1226..1226] *P*)) (CD:[1227..1229] 61)))))))))))) (.:[1229..1230] .))) ;sentence 9 Span:1231..1386 ;Screening for oncogene mutations using PCR, RFLP methods, and DNA sequencing ;was successfully completed for a high proportion of the available ;specimens. (SENT (S (NP-SBJ-1 (NP (NN:[1231..1240] Screening)) (PP (IN:[1241..1244] for) (NP (NP (NN:[1246..1254] oncogene) (NNS:[1255..1264] mutations)) (VP (VBG:[1265..1270] using) (NP (NP (NN:[1271..1274] PCR)) (,:[1274..1275] ,) (NP (NN:[1276..1280] RFLP) (NML (NNS:[1281..1288] methods))) (,:[1288..1289] ,) (CC:[1290..1293] and) (NP (NN:[1294..1297] DNA) (NN:[1298..1308] sequencing))))))) (VP (VBD:[1309..1312] was) (ADVP (RB:[1313..1325] successfully)) (VP (VBN:[1327..1336] completed) (NP-1 (-NONE-:[1336..1336] *)) (PP (IN:[1337..1340] for) (NP (NP (DT:[1341..1342] a) (JJ:[1343..1347] high) (NN:[1348..1358] proportion)) (PP (IN:[1359..1361] of) (NP (DT:[1362..1365] the) (JJ:[1366..1375] available) (NNS:[1376..1385] specimens))))))) (.:[1385..1386] .))) ;sentence 10 Span:1387..1555 ;Astrocytoma specimens from three children for whom screening with PCR was ;successfully completed were found to contain CAA-->GAA point mutations in ;K-ras at codon 61. ;[1387..1398]:malignancy-type:"Astrocytoma" ;[1421..1429]:malignancy-developmental-state:"children" ;[1508..1511]:variation-state-original:"CAA" ;[1514..1517]:variation-state-altered:"GAA" ;[1518..1533]:variation-type:"point mutations" ;[1537..1542]:gene-rna:"K-ras" ;[1546..1554]:variation-location:"codon 61" (SENT (S (NP-SBJ-2 (NP (NN:[1387..1398] Astrocytoma) (NNS:[1400..1409] specimens)) (PP (IN:[1410..1414] from) (NP (NP (CD:[1415..1420] three) (NNS:[1421..1429] children)) (SBAR (WHPP-1 (IN:[1430..1433] for) (WHNP (WP:[1434..1438] whom))) (S (NP-SBJ (NP (NN:[1439..1448] screening)) (PP (IN:[1449..1453] with) (NP (NN:[1454..1457] PCR)))) (VP (VBD:[1458..1461] was) (ADVP (RB:[1462..1474] successfully)) (VP (VBN:[1476..1485] completed) (PP-1 (-NONE-:[1485..1485] *T*))))))))) (VP (VBD:[1486..1490] were) (VP (VBN:[1491..1496] found) (S (NP-SBJ-2 (-NONE-:[1496..1496] *)) (VP (TO:[1497..1499] to) (VP (VB:[1500..1507] contain) (NP (NP (NML (NML (NN:[1508..1511] CAA)) (PP (SYM:[1511..1514] -->) (NP (NN:[1514..1517] GAA)))) (NN:[1518..1523] point) (NNS:[1524..1533] mutations)) (PP (IN:[1534..1536] in) (NP (NN:[1537..1542] K-ras)))) (PP-LOC (IN:[1543..1545] at) (NP (NN:[1546..1551] codon) (CD:[1552..1554] 61)))))))) (.:[1554..1555] .))) ;sentence 11 Span:1557..1629 ;None of the specimens contained mutations at any of the other locations. (SENT (S (NP-SBJ (NP (NN:[1557..1561] None)) (PP (IN:[1562..1564] of) (NP (DT:[1565..1568] the) (NNS:[1569..1578] specimens)))) (VP (VBD:[1579..1588] contained) (NP (NNS:[1589..1598] mutations)) (PP-LOC (IN:[1599..1601] at) (NP (NP (DT:[1602..1605] any)) (PP (IN:[1606..1608] of) (NP (DT:[1609..1612] the) (JJ:[1613..1618] other) (NNS:[1619..1628] locations)))))) (.:[1628..1629] .))) ;sentence 12 Span:1630..1738 ;These results, although preliminary, provide a potential clue for future ;mechanistic studies of CB tumors. ;[1728..1737]:malignancy-type:"CB tumors" (SENT (S (NP-SBJ (DT:[1630..1635] These) (NNS:[1637..1644] results)) (,:[1644..1645] ,) (PP (IN:[1646..1654] although) (NP (JJ:[1655..1666] preliminary))) (,:[1666..1667] ,) (VP (VBP:[1668..1675] provide) (NP (DT:[1676..1677] a) (JJ:[1678..1687] potential) (NN:[1688..1692] clue)) (PP (IN:[1693..1696] for) (NP (NP (JJ:[1697..1703] future) (JJ:[1704..1715] mechanistic) (NNS:[1717..1724] studies)) (PP (IN:[1725..1727] of) (NP (NN:[1728..1730] CB) (NNS:[1731..1737] tumors)))))) (.:[1737..1738] .))) ;sentence 13 Span:1739..1887 ;The possible roles of NNCs in inducing this mutation, or of this mutation as ;an early or late event in tumor progression, however, remain unclear. ;[1778..1791]:variation-event:"this mutation" ;[1800..1813]:variation-event:"this mutation" (SENT (S (NP-SBJ (NP (DT:[1739..1742] The) (JJ:[1743..1751] possible) (NNS:[1752..1757] roles)) (PP (PP (IN:[1758..1760] of) (NP (NP (NNS:[1761..1765] NNCs)) (PP (IN:[1766..1768] in) (S-NOM (NP-SBJ (-NONE-:[1768..1768] *)) (VP (VBG:[1769..1777] inducing) (NP (DT:[1778..1782] this) (NN:[1783..1791] mutation))))))) (,:[1791..1792] ,) (CC:[1793..1795] or) (PP (IN:[1797..1799] of) (NP (NP (DT:[1800..1804] this) (NN:[1805..1813] mutation)) (PP (IN:[1814..1816] as) (NP (NP (DT:[1817..1819] an) (NML (NML (JJ:[1820..1825] early) (NML-1 (-NONE-:[1825..1825] *P*))) (CC:[1826..1828] or) (NML (JJ:[1829..1833] late) (NML-1 (NN:[1834..1839] event))))) (PP (IN:[1840..1842] in) (NP (NN:[1843..1848] tumor) (NN:[1849..1860] progression))))))))) (,:[1860..1861] ,) (ADVP (RB:[1862..1869] however)) (,:[1869..1870] ,) (VP (VBP:[1871..1877] remain) (ADJP-PRD (JJ:[1879..1886] unclear))) (.:[1886..1887] .))) ;section 14 Span:1891..1935 ;PMID: 9107428 [PubMed - indexed for MEDLINE] (SEC (FRAG (NNP:[1891..1895] PMID) (::[1895..1896] :) (CD:[1897..1904] 9107428) (NN:[1905..1906] -LSB-) (NNP:[1906..1912] PubMed) (::[1913..1914] -) (NN:[1915..1922] indexed) (IN:[1923..1926] for) (NNP:[1927..1935] MEDLINE-RSB-)))