;PMID: 9327727 ;source_file_1307.mrg ;Release 0.9 of PennBioIE ;Funded by NSF ITR EIA-0205448 ;0)section:[e:0..34] = [t:0..34] ;1)sentence:[e:39..153] = [t:39..153] ;2)sentence:[e:154..214] = [t:154..214] ;3)section:[e:218..323] = [t:218..323] ;4)section:[e:327..414] = [t:327..414] ;5)sentence:[e:418..591] = [t:418..591] ;6)sentence:[e:592..810] = [t:592..810] ;7)sentence:[e:811..927] = [t:811..927] ;8)sentence:[e:928..1082] = [t:928..1082] ;9)sentence:[e:1083..1161] = [t:1083..1161] ;10)sentence:[e:1162..1394] = [t:1162..1394] ;11)sentence:[e:1395..1450] = [t:1395..1450] ;12)sentence:[e:1451..1596] = [t:1451..1596] ;13)sentence:[e:1598..1648] = [t:1598..1648] ;14)sentence:[e:1649..1853] = [t:1649..1853] ;15)section:[e:1857..1901] = [t:1857..1901] ;section 0 Span:0..34 ;Am J Pathol 1997 Oct;151(4):943-9 (SEC (FRAG (NNP:[0..2] Am) (NNP:[3..4] J) (NNP:[5..11] Pathol) (CD:[13..17] 1997) (CD:[18..25] Oct;151) (-LRB-:[25..26] -LRB-) (CD:[26..27] 4) (-RRB-:[27..28] -RRB-) (CD:[28..33] :943-) (CD:[33..34] 9))) ;sentence 1 Span:39..153 ;Can K-ras codon 12 mutations be used to distinguish benign bile duct ;proliferations from metastases in the liver? ;[43..48]:gene-rna:"K-ras" ;[49..57]:variation-location:"codon 12" ;[58..67]:variation-event:"mutations" ;[129..139]:malignancy-clinical-stage:"metastases" (SENT (SQ-HLN (MD:[39..42] Can) (NP-SBJ-1 (NN:[43..48] K-ras) (NML (NN:[49..54] codon) (CD:[55..57] 12)) (NNS:[58..67] mutations)) (VP (VB:[68..70] be) (VP (VBN:[71..75] used) (NP-1 (-NONE-:[75..75] *)) (S-ADV (NP-SBJ (-NONE-:[75..75] *)) (VP (TO:[76..78] to) (VP (VB:[79..90] distinguish) (NP (JJ:[91..97] benign) (NML (NN:[98..102] bile) (NN:[103..107] duct)) (NNS:[109..123] proliferations)) (PP (IN:[124..128] from) (NP (NP (NNS:[129..139] metastases)) (PP-LOC (IN:[140..142] in) (NP (DT:[143..146] the) (NN:[147..152] liver)))))))))) (.:[152..153] ?))) ;sentence 2 Span:154..214 ;A molecular analysis of 101 liver lesions from 93 patients. ;[182..196]:malignancy-type:"liver lesions" (SENT (NP (NP (DT:[154..155] A) (JJ:[156..165] molecular) (NN:[166..174] analysis)) (PP (IN:[175..177] of) (NP (NP (CD:[178..181] 101) (NN:[182..187] liver) (NNS:[189..196] lesions)) (PP (IN:[197..201] from) (NP (CD:[202..204] 93) (NNS:[205..213] patients))))) (.:[213..214] .))) ;section 3 Span:218..323 ;Hruban RH, Sturm PD, Slebos RJ, Wilentz RE, Musler AR, Yeo CJ, Sohn TA, van ;Velthuysen ML, Offerhaus GJ. (SEC (FRAG (NNP:[218..224] Hruban) (NNP:[225..227] RH) (,:[227..228] ,) (NNP:[229..234] Sturm) (NNP:[235..237] PD) (,:[237..238] ,) (NNP:[239..245] Slebos) (NNP:[246..248] RJ) (,:[248..249] ,) (NNP:[250..257] Wilentz) (NNP:[258..260] RE) (,:[260..261] ,) (NNP:[262..268] Musler) (NNP:[269..271] AR) (,:[271..272] ,) (NNP:[273..276] Yeo) (NNP:[277..279] CJ) (,:[279..280] ,) (NNP:[281..285] Sohn) (NNP:[286..288] TA) (,:[288..289] ,) (NNP:[290..293] van) (NNP:[295..305] Velthuysen) (NNP:[306..308] ML) (,:[308..309] ,) (NNP:[310..319] Offerhaus) (NNP:[320..323] GJ.))) ;section 4 Span:327..414 ;Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, ;Maryland, USA. (SEC (FRAG (NNP:[327..337] Department) (IN:[338..340] of) (NNP:[341..350] Pathology) (NNP:[350..351] ,) (NNP:[352..357] Johns) (NNP:[358..365] Hopkins) (NNP:[366..373] Medical) (NNP:[374..386] Institutions) (,:[386..387] ,) (NNP:[388..397] Baltimore) (,:[397..398] ,) (NNP:[400..408] Maryland) (,:[408..409] ,) (NNP:[410..413] USA) (.:[413..414] .))) ;sentence 5 Span:418..591 ;It can be difficult to distinguish benign bile duct proliferations (BDPs) ;from well-differentiated metastatic peripancreatic adenocarcinomas on ;histological grounds alone. ;[518..528]:malignancy-clinical-stage:"metastatic" ;[529..559]:malignancy-type:"peripancreatic adenocarcinomas" (SENT (S (NP-SBJ (PRP:[418..420] It)) (VP (MD:[421..424] can) (VP (VB:[425..427] be) (ADJP-PRD (JJ:[428..437] difficult) (S (NP-SBJ (-NONE-:[437..437] *)) (VP (TO:[438..440] to) (VP (VB:[441..452] distinguish) (NP (JJ:[453..459] benign) (NML (NML (NML (NN:[460..464] bile) (NN:[465..469] duct)) (NNS:[470..484] proliferations)) (NML (-LRB-:[485..486] -LRB-) (NP (NNS:[486..490] BDPs)) (-RRB-:[490..491] -RRB-)))) (PP (IN:[492..496] from) (NP (ADJP (RB:[498..502] well) (HYPH:[502..503] -) (VBN:[503..517] differentiated)) (JJ:[518..528] metastatic) (JJ:[529..543] peripancreatic) (NNS:[544..559] adenocarcinomas))) (PP (IN:[560..562] on) (NP (JJ:[563..575] histological) (NNS:[577..584] grounds) (ADVP (RB:[585..590] alone)))))))))) (.:[590..591] .))) ;sentence 6 Span:592..810 ;Most peripancreatic carcinomas harbor activating point mutations in codon 12 ;of the K-ras oncogene, suggesting that K-ras mutational status may provide a ;molecular basis for distinguishing BDPs from liver metastases. ;[597..622]:malignancy-type:"peripancreatic carcinomas" ;[641..656]:variation-type:"point mutations" ;[661..669]:variation-location:"codon 12" ;[677..682]:gene-rna:"K-ras" ;[709..714]:gene-rna:"K-ras" ;[793..798]:malignancy-type:"liver" ;[799..809]:malignancy-clinical-stage:"metastases" (SENT (S (NP-SBJ (JJS:[592..596] Most) (JJ:[597..611] peripancreatic) (NNS:[612..622] carcinomas)) (VP (VBP:[623..629] harbor) (NP (VBG:[630..640] activating) (NN:[641..646] point) (NNS:[647..656] mutations)) (PP-LOC (IN:[658..660] in) (NP (NP (NN:[661..666] codon) (CD:[667..669] 12)) (PP (IN:[670..672] of) (NP (DT:[673..676] the) (NN:[677..682] K-ras) (NN:[683..691] oncogene))))) (,:[691..692] ,) (S-ADV (NP-SBJ (-NONE-:[692..692] *)) (VP (VBG:[693..703] suggesting) (SBAR (IN:[704..708] that) (S (NP-SBJ (NN:[709..714] K-ras) (JJ:[715..725] mutational) (NN:[726..732] status)) (VP (MD:[733..736] may) (VP (VB:[738..745] provide) (NP (NP (DT:[746..747] a) (JJ:[748..757] molecular) (NN:[758..763] basis)) (PP (IN:[764..767] for) (S-NOM (NP-SBJ (-NONE-:[767..767] *)) (VP (VBG:[768..782] distinguishing) (NP (NNS:[783..787] BDPs)) (PP (IN:[788..792] from) (NP (NN:[793..798] liver) (NNS:[799..809] metastases)))))))))))))) (.:[809..810] .))) ;sentence 7 Span:811..927 ;The ability of tests for mutations in codon 12 of K-ras to make this ;distinction was examined in a two-part study. ;[837..846]:variation-event:"mutations" ;[850..858]:variation-location:"codon 12" ;[862..867]:gene-rna:"K-ras" (SENT (S (NP-SBJ-2 (NP (DT:[811..814] The) (NN:[816..823] ability) (S-1 (-NONE-:[823..823] *ICH*))) (PP (IN:[824..826] of) (NP (NP (NNS:[827..832] tests)) (PP (IN:[833..836] for) (NP (NP (NNS:[837..846] mutations)) (PP-LOC (IN:[847..849] in) (NP (NP (NN:[850..855] codon) (CD:[856..858] 12)) (PP (IN:[859..861] of) (NP (NN:[862..867] K-ras))))))))) (S-1 (NP-SBJ (-NONE-:[867..867] *)) (VP (TO:[868..870] to) (VP (VB:[871..875] make) (NP (DT:[876..880] this) (NN:[881..892] distinction)))))) (VP (VBD:[893..896] was) (VP (VBN:[898..906] examined) (NP-2 (-NONE-:[906..906] *)) (PP (IN:[907..909] in) (NP (DT:[910..911] a) (NML (CD:[912..915] two) (HYPH:[915..916] -) (NN:[916..920] part)) (NN:[921..926] study))))) (.:[926..927] .))) ;sentence 8 Span:928..1082 ;In the first part we determined the K-ras mutational status of 56 liver ;lesions and 48 primary peripancreatic adenocarcinomas obtained from 48 ;patients. ;[964..969]:gene-rna:"K-ras" ;[995..1008]:malignancy-type:"liver lesions" ;[1016..1023]:malignancy-clinical-stage:"primary" ;[1024..1055]:malignancy-type:"peripancreatic adenocarcinomas" (SENT (S (PP (IN:[928..930] In) (NP (DT:[931..934] the) (JJ:[935..940] first) (NN:[941..945] part))) (NP-SBJ (PRP:[946..948] we)) (VP (VBD:[949..959] determined) (NP (NP (DT:[960..963] the) (NML (NN:[964..969] K-ras)) (JJ:[971..981] mutational) (NN:[982..988] status)) (PP (IN:[989..991] of) (NP (NP (NP (CD:[992..994] 56) (NN:[995..1000] liver) (NNS:[1001..1008] lesions)) (CC:[1009..1012] and) (NP (CD:[1013..1015] 48) (JJ:[1016..1023] primary) (JJ:[1024..1038] peripancreatic) (NNS:[1040..1055] adenocarcinomas))) (VP (VBN:[1056..1064] obtained) (NP (-NONE-:[1064..1064] *)) (PP (IN:[1065..1069] from) (NP (CD:[1070..1072] 48) (NNS:[1073..1081] patients)))))))) (.:[1081..1082] .))) ;sentence 9 Span:1083..1161 ;In the second part of this study an additional 45 liver lesions were ;studied. ;[1134..1147]:malignancy-type:"liver lesions" (SENT (S (PP (IN:[1083..1085] In) (NP (NP (DT:[1086..1089] the) (JJ:[1090..1096] second) (NN:[1097..1101] part)) (PP (IN:[1102..1104] of) (NP (DT:[1105..1109] this) (NN:[1110..1115] study))))) (NP-SBJ-1 (DT:[1116..1118] an) (JJ:[1120..1130] additional) (CD:[1131..1133] 45) (NN:[1134..1139] liver) (NNS:[1140..1147] lesions)) (VP (VBD:[1148..1152] were) (VP (VBN:[1153..1160] studied) (NP-1 (-NONE-:[1160..1160] *)))) (.:[1160..1161] .))) ;sentence 10 Span:1162..1394 ;In the first 48 patients, activating point mutations in codon 12 of K-ras ;were detected in 28 (61%) of the 46 primary carcinomas, in 8 (100%) of 8 ;liver metastases, in 2 (6.5%) of 31 BDPs, and in none (0%) of 14 liver ;granulomas. ;[1200..1215]:variation-type:"point mutations" ;[1219..1227]:variation-location:"codon 12" ;[1231..1236]:gene-rna:"K-ras" ;[1273..1280]:malignancy-clinical-stage:"primary" ;[1282..1292]:malignancy-type:"carcinomas" ;[1311..1316]:malignancy-type:"liver" ;[1317..1327]:malignancy-clinical-stage:"metastases" ;[1377..1393]:malignancy-type:"liver granulomas" (SENT (S (PP (IN:[1162..1164] In) (NP (DT:[1165..1168] the) (JJ:[1169..1174] first) (CD:[1175..1177] 48) (NNS:[1178..1186] patients))) (,:[1186..1187] ,) (NP-SBJ-1 (NP (VBG:[1188..1198] activating) (NN:[1200..1205] point) (NNS:[1206..1215] mutations)) (PP-LOC (IN:[1216..1218] in) (NP (NP (NN:[1219..1224] codon) (CD:[1225..1227] 12)) (PP (IN:[1228..1230] of) (NP (NN:[1231..1236] K-ras)))))) (VP (VBD:[1237..1241] were) (VP (VBN:[1242..1250] detected) (NP-1 (-NONE-:[1250..1250] *)) (PP-LOC (PP (IN:[1251..1253] in) (NP (NP (CD:[1254..1256] 28) (PRN (-LRB-:[1257..1258] -LRB-) (NP (CD:[1258..1260] 61) (NN:[1260..1261] %)) (-RRB-:[1261..1262] -RRB-))) (PP (IN:[1263..1265] of) (NP (DT:[1266..1269] the) (CD:[1270..1272] 46) (JJ:[1273..1280] primary) (NNS:[1282..1292] carcinomas))))) (,:[1292..1293] ,) (PP (IN:[1294..1296] in) (NP (NP (CD:[1297..1298] 8) (PRN (-LRB-:[1299..1300] -LRB-) (NP (CD:[1300..1303] 100) (NN:[1303..1304] %) (-RRB-:[1304..1305] -RRB-)))) (PP (IN:[1306..1308] of) (NP (CD:[1309..1310] 8) (NN:[1311..1316] liver) (NNS:[1317..1327] metastases))))) (,:[1327..1328] ,) (PP (IN:[1329..1331] in) (NP (NP (CD:[1332..1333] 2) (PRN (-LRB-:[1334..1335] -LRB-) (NP (CD:[1335..1338] 6.5) (NN:[1338..1339] %)) (-RRB-:[1339..1340] -RRB-))) (PP (IN:[1341..1343] of) (NP (CD:[1344..1346] 31) (NNS:[1347..1351] BDPs))))) (,:[1351..1352] ,) (CC:[1353..1356] and) (PP (IN:[1357..1359] in) (NP (NP (NN:[1361..1365] none) (PRN (-LRB-:[1366..1367] -LRB-) (NP (CD:[1367..1368] 0) (NN:[1368..1369] %)) (-RRB-:[1369..1370] -RRB-))) (PP (IN:[1371..1373] of) (NP (CD:[1374..1376] 14) (NN:[1377..1382] liver) (NNS:[1383..1393] granulomas)))))))) (.:[1393..1394] .))) ;sentence 11 Span:1395..1450 ;Three BDPs and two primary carcinomas did not amplify. ;[1414..1421]:malignancy-clinical-stage:"primary" ;[1422..1432]:malignancy-type:"carcinomas" (SENT (S (NP-SBJ (NP (CD:[1395..1400] Three) (NNS:[1401..1405] BDPs)) (CC:[1406..1409] and) (NP (CD:[1410..1413] two) (JJ:[1414..1421] primary) (NNS:[1422..1432] carcinomas))) (VP (VBD:[1433..1436] did) (RB:[1437..1440] not) (VP (VB:[1442..1449] amplify))) (.:[1449..1450] .))) ;sentence 12 Span:1451..1596 ;To further estimate the prevalence of K-ras mutations in BDPs we analyzed an ;additional series of 45 mostly incidental BDPs for K-ras mutations. ;[1489..1494]:gene-rna:"K-ras" ;[1580..1585]:gene-rna:"K-ras" (SENT (S (S-PRP (NP-SBJ (-NONE-:[1451..1451] *)) (VP (TO:[1451..1453] To) (ADVP (RB:[1454..1461] further)) (VP (VB:[1462..1470] estimate) (NP (NP (DT:[1471..1474] the) (NN:[1475..1485] prevalence)) (PP (IN:[1486..1488] of) (NP (NP (NN:[1489..1494] K-ras) (NNS:[1495..1504] mutations)) (PP-LOC (IN:[1505..1507] in) (NP (NNS:[1508..1512] BDPs))))))))) (NP-SBJ (PRP:[1513..1515] we)) (VP (VBD:[1517..1525] analyzed) (NP (NP (DT:[1526..1528] an) (JJ:[1529..1539] additional) (NN:[1540..1546] series)) (PP (IN:[1547..1549] of) (NP (NP (CD:[1550..1552] 45) (ADJP (RB:[1553..1559] mostly) (JJ:[1560..1570] incidental)) (NNS:[1571..1575] BDPs)) (PP (IN:[1576..1579] for) (NP (NN:[1580..1585] K-ras) (NNS:[1586..1595] mutations))))))) (.:[1595..1596] .))) ;sentence 13 Span:1598..1648 ;Three (6.7%) of these 45 harbored K-ras mutations. ;[1632..1637]:gene-rna:"K-ras" (SENT (S (NP-SBJ (NP (CD:[1598..1603] Three) (PRN (-LRB-:[1604..1605] -LRB-) (NP (CD:[1605..1608] 6.7) (NN:[1608..1609] %)) (-RRB-:[1609..1610] -RRB-))) (PP (IN:[1611..1613] of) (NP (DT:[1614..1619] these) (CD:[1620..1622] 45)))) (VP (VBD:[1623..1631] harbored) (NP (NN:[1632..1637] K-ras) (NNS:[1638..1647] mutations))) (.:[1647..1648] .))) ;sentence 14 Span:1649..1853 ;These results suggest that K-ras mutations may be useful in distinguishing ;BDPs from metastases in the liver; however, there is some overlap in the ;mutational spectra of BDPs and pancreatic carcinomas. ;[1677..1682]:gene-rna:"K-ras" ;[1735..1745]:malignancy-clinical-stage:"metastases" ;[1831..1852]:malignancy-type:"pancreatic carcinomas" (SENT (S (NP-SBJ (DT:[1649..1654] These) (NNS:[1655..1662] results)) (VP (VBP:[1663..1670] suggest) (SBAR (IN:[1671..1675] that) (S (NP-SBJ (NN:[1677..1682] K-ras) (NNS:[1683..1692] mutations)) (VP (MD:[1693..1696] may) (VP (VB:[1697..1699] be) (ADJP-PRD (JJ:[1700..1706] useful)) (PP (IN:[1707..1709] in) (S-NOM (NP-SBJ (-NONE-:[1709..1709] *)) (VP (VBG:[1710..1724] distinguishing) (NP (NNS:[1725..1729] BDPs)) (PP (IN:[1730..1734] from) (NP (NP (NNS:[1735..1745] metastases)) (PP (IN:[1746..1748] in) (NP (DT:[1749..1752] the) (NN:[1754..1759] liver)))))))))))) (::[1759..1760] ;) (S-ADV (ADVP (RB:[1761..1768] however)) (,:[1768..1769] ,) (NP-SBJ (EX:[1770..1775] there)) (VP (VBZ:[1776..1778] is) (NP-PRD (DT:[1779..1783] some) (NN:[1784..1791] overlap)) (PP (IN:[1792..1794] in) (NP (NP (DT:[1795..1798] the) (JJ:[1799..1809] mutational) (NNS:[1810..1817] spectra)) (PP (IN:[1818..1820] of) (NP (NP (NNS:[1821..1825] BDPs)) (CC:[1826..1829] and) (NP (JJ:[1831..1841] pancreatic) (NNS:[1842..1852] carcinomas))))))))) (.:[1852..1853] .))) ;section 15 Span:1857..1901 ;PMID: 9327727 [PubMed - indexed for MEDLINE] (SEC (FRAG (NNP:[1857..1861] PMID) (::[1861..1862] :) (CD:[1863..1870] 9327727) (NN:[1871..1872] -LSB-) (NNP:[1872..1878] PubMed) (::[1879..1880] -) (NN:[1881..1888] indexed) (IN:[1889..1892] for) (NNP:[1893..1901] MEDLINE-RSB-)))