;PMID: 10485468 ;source_file_1213.mrg ;Release 0.9 of PennBioIE ;Funded by NSF ITR EIA-0205448 ;0)section:[e:0..37] = [t:0..37] ;1)sentence:[e:42..129] = [t:42..129] ;2)section:[e:133..230] = [t:133..230] ;3)section:[e:234..340] = [t:234..340] ;4)sentence:[e:344..542] = [t:344..542] ;5)sentence:[e:543..745] = [t:543..745] ;6)sentence:[e:746..877] = [t:746..877] ;7)sentence:[e:878..1068] = [t:878..1068] ;8)sentence:[e:1069..1351] = [t:1069..1351] ;9)sentence:[e:1352..1556] = [t:1352..1556] ;10)section:[e:1560..1605] = [t:1560..1605] ;section 0 Span:0..37 ;Cancer Res 1999 Sep 1;59(17):4257-60 (SEC (FRAG (NN:[0..6] Cancer) (NNP:[7..10] Res) (CD:[12..16] 1999) (NNP:[17..20] Sep) (CD:[21..26] 1;59-LRB-) (CD:[26..28] 17) (-RRB-:[28..29] -RRB-) (CD:[29..34] :4257) (NN:[34..35] -) (CD:[35..37] 60))) ;sentence 1 Span:42..129 ;Frequent somatic mutations of the beta-catenin gene in intestinal-type ;gastric cancer. ;[76..88]:gene-rna:"beta-catenin" ;[97..128]:malignancy:"intestinal-type gastric cancer" (SENT (NP-HLN (NP (JJ:[42..50] Frequent) (JJ:[51..58] somatic) (NNS:[59..68] mutations)) (PP (IN:[69..71] of) (NP (DT:[72..75] the) (NN:[76..88] beta-catenin) (NN:[89..93] gene))) (PP (IN:[94..96] in) (NP (NML (JJ:[97..107] intestinal) (HYPH:[107..108] -) (NN:[108..112] type)) (JJ:[113..120] gastric) (NN:[122..128] cancer))) (.:[128..129] .))) ;section 2 Span:133..230 ;Park WS, Oh RR, Park JY, Lee SH, Shin MS, Kim YS, Kim SY, Lee HK, Kim PJ, Oh ;ST, Yoo NJ, Lee JY. (SEC (FRAG (NNP:[133..137] Park) (NNP:[138..140] WS) (,:[140..141] ,) (NNP:[142..144] Oh) (NNP:[145..147] RR) (,:[147..148] ,) (NNP:[149..153] Park) (NNP:[154..156] JY) (NNP:[156..157] ,) (NNP:[158..161] Lee) (NNP:[162..164] SH) (,:[164..165] ,) (NNP:[166..170] Shin) (NNP:[171..173] MS) (,:[173..174] ,) (NNP:[175..178] Kim) (NNP:[179..181] YS) (,:[181..182] ,) (NNP:[183..186] Kim) (NNP:[187..189] SY) (,:[189..190] ,) (NNP:[191..194] Lee) (NNP:[195..197] HK) (,:[197..198] ,) (NNP:[199..202] Kim) (NNP:[203..205] PJ) (,:[205..206] ,) (NNP:[207..209] Oh) (NNP:[210..212] ST) (,:[212..213] ,) (NNP:[215..218] Yoo) (NNP:[219..221] NJ) (,:[221..222] ,) (NNP:[223..226] Lee) (NNP:[227..229] JY) (.:[229..230] .))) ;section 3 Span:234..340 ;Department of Pathology and Cancer Research Institute, Catholic University ;Medical College, Seoul, Korea. (SEC (FRAG (NNP:[234..244] Department) (IN:[245..247] of) (NNP:[248..257] Pathology) (CC:[258..261] and) (NNP:[262..268] Cancer) (NNP:[269..277] Research) (NNP:[278..287] Institute) (IN:[287..288] ,) (NNP:[289..297] Catholic) (NNP:[298..308] University) (NNP:[310..317] Medical) (NNP:[318..325] College) (,:[325..326] ,) (NNP:[327..332] Seoul) (,:[332..333] ,) (NNP:[334..339] Korea) (.:[339..340] .))) ;sentence 4 Span:344..542 ;The increased level of cytoplasmic beta-catenin through the mutations to ;either beta-catenin or adenomatous polyposis coli (APC) has been proposed as ;an important oncogenic step in various tumors. ;[379..391]:gene-generic:"beta-catenin" ;[425..437]:gene-rna:"beta-catenin" ;[441..467]:gene-rna:"adenomatous polyposis coli" ;[469..472]:gene-rna:"APC" (SENT (S (NP-SBJ-1 (NP (DT:[344..347] The) (VBN:[348..357] increased) (NN:[358..363] level)) (PP (IN:[364..366] of) (NP (JJ:[367..378] cytoplasmic) (NN:[379..391] beta-catenin))) (PP (IN:[392..399] through) (NP (NP (DT:[400..403] the) (NNS:[404..413] mutations)) (PP (TO:[414..416] to) (NP (CC:[417..423] either) (NP (NN:[425..437] beta-catenin)) (CC:[438..440] or) (NP (NP (JJ:[441..452] adenomatous) (NN:[453..462] polyposis) (NN:[463..467] coli)) (NP (-LRB-:[468..469] -LRB-) (NN:[469..472] APC) (-RRB-:[472..473] -RRB-)))))))) (VP (VBZ:[474..477] has) (VP (VBN:[478..482] been) (VP (VBN:[483..491] proposed) (NP-1 (-NONE-:[491..491] *)) (PP (IN:[492..494] as) (NP (NP (DT:[495..497] an) (JJ:[499..508] important) (JJ:[509..518] oncogenic) (NN:[519..523] step)) (PP (IN:[524..526] in) (NP (JJ:[527..534] various) (NNS:[535..541] tumors)))))))) (.:[541..542] .))) ;sentence 5 Span:543..745 ;Gastric cancer showed frequent genetic alterations of the APC gene, and the ;risk for gastric cancer in familial adenomatosus polyposis patients is 10 ;times higher than that in the general population. ;[543..557]:malignancy:"Gastric cancer" ;[602..605]:gene-rna:"APC" ;[629..643]:malignancy:"gastric cancer" ;[647..679]:malignancy:"familial adenomatosus polyposis" (SENT (S (S (NP-SBJ (JJ:[543..550] Gastric) (NN:[551..557] cancer)) (VP (VBD:[558..564] showed) (NP (NP (JJ:[565..573] frequent) (JJ:[575..582] genetic) (NNS:[583..594] alterations)) (PP (IN:[595..597] of) (NP (DT:[598..601] the) (NN:[602..605] APC) (NN:[606..610] gene)))))) (,:[610..611] ,) (CC:[612..615] and) (S (NP-SBJ (NP (DT:[616..619] the) (NN:[620..624] risk)) (PP (IN:[625..628] for) (NP (JJ:[629..636] gastric) (NN:[637..643] cancer))) (PP (IN:[644..646] in) (NP (JJ:[647..655] familial) (JJ:[657..669] adenomatosus) (NN:[670..679] polyposis) (NNS:[680..688] patients)))) (VP (VBZ:[689..691] is) (ADJP-PRD (ADJP (NP (CD:[692..694] 10) (NNS:[695..700] times)) (JJR:[701..707] higher)) (PP (IN:[708..712] than) (NP (NP (DT:[713..717] that)) (PP (IN:[718..720] in) (NP (DT:[721..724] the) (JJ:[725..732] general) (NN:[734..744] population)))))))) (.:[744..745] .))) ;sentence 6 Span:746..877 ;These findings raise the possibility that mutations of beta-catenin may also ;be associated with the development of gastric cancer. ;[801..813]:gene-rna:"beta-catenin" ;[862..876]:malignancy:"gastric cancer" (SENT (S (NP-SBJ (DT:[746..751] These) (NNS:[752..760] findings)) (VP (VBP:[761..766] raise) (NP (NP (DT:[767..770] the) (NN:[771..782] possibility)) (SBAR (IN:[783..787] that) (S (NP-SBJ-1 (NP (NNS:[788..797] mutations)) (PP (IN:[798..800] of) (NP (NN:[801..813] beta-catenin)))) (VP (MD:[815..818] may) (ADVP (RB:[819..823] also)) (VP (VB:[824..826] be) (VP (VBN:[827..837] associated) (NP-1 (-NONE-:[837..837] *)) (PP-CLR (IN:[838..842] with) (NP (NP (DT:[843..846] the) (NN:[847..858] development)) (PP (IN:[859..861] of) (NP (JJ:[862..869] gastric) (NN:[870..876] cancer)))))))))))) (.:[876..877] .))) ;sentence 7 Span:878..1068 ;We detected seven somatic mutations in a portion of exon 3 encoding for the ;glycogen synthase kinase 3beta phosphorylation consensus region of the ;beta-catenin gene in 43 gastric cancers. ;[905..914]:variation-event:"mutations" ;[931..937]:variation-location:"exon 3" ;[955..986]:gene-protein:"glycogen synthase kinase 3beta" ;[1027..1039]:gene-rna:"beta-catenin" ;[1052..1067]:malignancy:"gastric cancers" (SENT (S (NP-SBJ (PRP:[878..880] We)) (VP (VBD:[881..889] detected) (NP (NP (CD:[890..895] seven) (JJ:[897..904] somatic) (NNS:[905..914] mutations)) (PP (IN:[915..917] in) (NP (NP (DT:[918..919] a) (NN:[920..927] portion)) (PP (IN:[928..930] of) (NP (NP (NN:[931..935] exon) (CD:[936..937] 3)) (VP (VBG:[938..946] encoding) (PP-CLR (IN:[947..950] for) (NP (NP (DT:[951..954] the) (NML (NN:[955..963] glycogen) (NN:[964..972] synthase) (NN:[974..980] kinase) (NN:[981..986] 3beta)) (NN:[987..1002] phosphorylation) (NN:[1003..1012] consensus) (NN:[1013..1019] region)) (PP (IN:[1020..1022] of) (NP (DT:[1023..1026] the) (NN:[1027..1039] beta-catenin) (NN:[1040..1044] gene))))))))))) (PP (IN:[1045..1047] in) (NP (CD:[1048..1050] 43) (JJ:[1052..1059] gastric) (NNS:[1060..1067] cancers)))) (.:[1067..1068] .))) ;sentence 8 Span:1069..1351 ;All of these mutations were missense mutations, of which five are in the ;highly conserved aspartic acid 32 and two are in serine 29; all of these ;seven mutations were detected exclusively in intestinal-type gastric cancers ;(7 of 26; 26.9%), but not in the diffuse-type (0 of 17). ;[1082..1091]:variation-event:"mutations" ;[1097..1115]:variation-type:"missense mutations" ;[1160..1173]:variation-state-original:"aspartic acid" ;[1174..1176]:variation-location:"32" ;[1192..1198]:variation-state-original:"serine" ;[1199..1201]:variation-location:"29" ;[1223..1232]:variation-event:"mutations" ;[1262..1294]:malignancy:"intestinal-type gastric cancers" ;[1278..1294]...[1328..1340]:malignancy:"gastric cancers"..."diffuse-type" (SENT (S (S (NP-SBJ (NP (DT:[1069..1072] All)) (PP (IN:[1073..1075] of) (NP (DT:[1076..1081] these) (NNS:[1082..1091] mutations)))) (VP (VBD:[1092..1096] were) (NP-PRD (NP (JJ:[1097..1105] missense) (NNS:[1106..1115] mutations)) (,:[1115..1116] ,) (SBAR (WHPP-1 (IN:[1117..1119] of) (WHNP (WDT:[1120..1125] which))) (S (S (NP-SBJ (NP (CD:[1126..1130] five)) (PP-1 (-NONE-:[1130..1130] *T*))) (VP (VBP:[1132..1135] are) (PP-PRD (IN:[1136..1138] in) (NP (DT:[1139..1142] the) (ADJP (RB:[1143..1149] highly) (VBN:[1150..1159] conserved)) (NML (JJ:[1160..1168] aspartic) (NN:[1169..1173] acid)) (CD:[1174..1176] 32))))) (CC:[1177..1180] and) (S (NP-SBJ (NP (CD:[1181..1184] two)) (PP-1 (-NONE-:[1184..1184] *T*))) (VP (VBP:[1185..1188] are) (PP-PRD (IN:[1189..1191] in) (NP (NN:[1192..1198] serine) (CD:[1199..1201] 29)))))))))) (::[1201..1202] ;) (S (NP-SBJ-2 (NP (DT:[1203..1206] all)) (PP (IN:[1207..1209] of) (NP (DT:[1211..1216] these) (CD:[1217..1222] seven) (NNS:[1223..1232] mutations)))) (VP (VBD:[1233..1237] were) (VP (VP (VBN:[1238..1246] detected) (NP-2 (-NONE-:[1246..1246] *)) (ADVP=3 (RB:[1247..1258] exclusively)) (PP-LOC=4 (IN:[1259..1261] in) (NP (NML (JJ:[1262..1272] intestinal) (HYPH:[1272..1273] -) (NN:[1273..1277] type)) (JJ:[1278..1285] gastric) (NNS:[1287..1294] cancers) (PRN (-LRB-:[1295..1296] -LRB-) (FRAG (NP (NP (CD:[1296..1297] 7)) (PP (IN:[1298..1300] of) (NP (CD:[1301..1303] 26)))) (::[1303..1304] ;) (NP (CD:[1305..1309] 26.9) (NN:[1309..1310] %))) (-RRB-:[1310..1311] -RRB-))))) (,:[1311..1312] ,) (CC:[1313..1316] but) (VP (RB:[1317..1320] not) (ADVP=3 (-NONE-:[1320..1320] *NOT*)) (PP-LOC=4 (IN:[1321..1323] in) (NP (DT:[1324..1327] the) (JJ:[1328..1335] diffuse) (HYPH:[1335..1336] -) (NN:[1336..1340] type) (PRN (-LRB-:[1341..1342] -LRB-) (NP (NP (CD:[1342..1343] 0)) (PP (IN:[1344..1346] of) (NP (CD:[1347..1349] 17)))) (-RRB-:[1349..1350] -RRB-)))))))) (.:[1350..1351] .))) ;sentence 9 Span:1352..1556 ;We concluded that disruption of the APC/beta-catenin/T cell factor-lymphoid ;enhancer binding factor pathway might play an important role especially in ;the development of intestinal-type gastric cancer. ;[1389..1392]:gene-generic:"APC" ;[1393..1405]:gene-generic:"beta-catenin" ;[1406..1419]:gene-protein:"T cell factor" ;[1420..1453]:gene-protein:"lymphoid enhancer binding factor" ;[1525..1555]:malignancy:"intestinal-type gastric cancer" (SENT (S (NP-SBJ (PRP:[1352..1354] We)) (VP (VBD:[1355..1364] concluded) (SBAR (IN:[1366..1370] that) (S (NP-SBJ (NP (NN:[1371..1381] disruption)) (PP (IN:[1382..1384] of) (NP (DT:[1385..1388] the) (NML (NML (NN:[1389..1392] APC)) (SYM:[1392..1393] /) (NML (NN:[1393..1405] beta-catenin)) (SYM:[1405..1406] /) (NML (NN:[1406..1407] T) (NN:[1408..1412] cell) (NN:[1413..1419] factor)) (HYPH:[1419..1420] -) (NML (NML (JJ:[1420..1428] lymphoid) (NN:[1429..1437] enhancer)) (VBG:[1438..1445] binding) (NN:[1447..1453] factor))) (NN:[1454..1461] pathway)))) (VP (MD:[1462..1467] might) (VP (VB:[1468..1472] play) (NP (DT:[1473..1475] an) (JJ:[1476..1485] important) (NN:[1486..1490] role)) (PP (ADVP (RB:[1491..1501] especially)) (IN:[1502..1504] in) (NP (NP (DT:[1505..1508] the) (NN:[1509..1520] development)) (PP (IN:[1521..1523] of) (NP (NML (JJ:[1525..1535] intestinal) (HYPH:[1535..1536] -) (NN:[1536..1540] type)) (JJ:[1541..1548] gastric) (NN:[1549..1555] cancer)))))))))) (.:[1555..1556] .))) ;section 10 Span:1560..1605 ;PMID: 10485468 [PubMed - indexed for MEDLINE] (SEC (FRAG (NNP:[1560..1564] PMID) (::[1564..1565] :) (CD:[1566..1574] 10485468) (IN:[1575..1576] -LSB-) (NNP:[1576..1582] PubMed) (HYPH:[1583..1584] -) (JJ:[1585..1592] indexed) (IN:[1593..1596] for) (NNP:[1597..1605] MEDLINE-RSB-)))