;PMID: 10197610 ;source_file_1215.mrg ;Release 0.9 of PennBioIE ;Funded by NSF ITR EIA-0205448 ;0)section:[e:0..35] = [t:0..35] ;1)sentence:[e:40..159] = [t:40..159] ;2)section:[e:163..231] = [t:163..231] ;3)section:[e:235..330] = [t:235..330] ;4)sentence:[e:334..636] = [t:334..636] ;5)sentence:[e:637..744] = [t:637..744] ;6)sentence:[e:745..898] = [t:745..898] ;7)sentence:[e:899..1059] = [t:899..1059] ;8)sentence:[e:1060..1255] = [t:1060..1255] ;9)sentence:[e:1256..1371] = [t:1256..1371] ;10)sentence:[e:1372..1616] = [t:1372..1616] ;11)sentence:[e:1617..1806] = [t:1617..1806] ;12)section:[e:1810..1855] = [t:1810..1855] ;section 0 Span:0..35 ;Cancer Res 1999 Apr 1;59(7):1442-4 (SEC (FRAG (NN:[0..6] Cancer) (NNP:[7..10] Res) (CD:[12..16] 1999) (.:[17..20] Apr) (CD:[21..26] 1;59-LRB-) (CD:[26..28] 7-RRB-) (CD:[28..33] :1442) (::[33..34] -) (CD:[34..35] 4))) ;sentence 1 Span:40..159 ;Beta-catenin mutations are more frequent in small colorectal adenomas than in ; larger adenomas and invasive carcinomas. ;[40..52]:gene-rna:"Beta-catenin" ;[84..109]:malignancy:"small colorectal adenomas" ;[119..134]:malignancy:"larger adenomas" ;[139..158]:malignancy:"invasive carcinomas" (SENT (S (NP-SBJ (NN:[40..52] Beta-catenin) (NNS:[53..62] mutations)) (VP (VBP:[63..66] are) (ADJP-PRD (ADJP (RBR:[67..71] more) (JJ:[72..80] frequent)) (PP-1 (-NONE-:[80..80] *ICH*))) (PP-LOC (IN:[81..83] in) (NP (JJ:[84..89] small) (JJ:[90..100] colorectal) (NNS:[101..109] adenomas))) (PP-1 (IN:[110..114] than) (PP (IN:[115..117] in) (NP (NP (JJR:[119..125] larger) (NNS:[126..134] adenomas)) (CC:[135..138] and) (NP (JJ:[139..147] invasive) (NNS:[148..158] carcinomas)))))) (.:[158..159] .))) ;section 2 Span:163..231 ;Samowitz WS, Powers MD, Spirio LN, Nollet F, van Roy F, Slattery ML. (SEC (FRAG (NNP:[163..171] Samowitz) (NNP:[172..174] WS) (,:[174..175] ,) (NNP:[176..182] Powers) (NNP:[183..185] MD) (,:[185..186] ,) (NNP:[187..193] Spirio) (NNP:[194..196] LN) (,:[196..197] ,) (NNP:[198..204] Nollet) (NNP:[205..206] F) (,:[206..207] ,) (NNP:[208..211] van) (NNP:[212..215] Roy) (NNP:[216..217] F) (,:[217..218] ,) (NNP:[219..227] Slattery) (NNP:[228..231] ML.))) ;section 3 Span:235..330 ;Department of Pathology, University of Utah Health Sciences Center, Salt Lake ; City 84132, USA. (SEC (FRAG (NNP:[235..245] Department) (IN:[246..248] of) (NNP:[249..258] Pathology) (,:[258..259] ,) (NNP:[260..270] University) (IN:[271..273] of) (NNP:[274..278] Utah) (NNP:[279..285] Health) (NNP:[286..294] Sciences) (NNP:[295..301] Center) (,:[301..302] ,) (NNP:[303..307] Salt) (NNP:[308..312] Lake) (NNP:[314..318] City) (POS:[319..324] 84132) (NNPS:[324..325] ,) (NNP:[326..329] USA) (.:[329..330] .))) ;sentence 4 Span:334..636 ;Loss of serine or threonine phosphorylation sites from exon 3 of beta-catenin ; has been identified in approximately half of colorectal tumors which lack ;adenomatous polyposis coli (APC) mutations, but the overall contribution of ;beta-catenin mutations to sporadic colorectal tumorigenesis is unclear. ;[389..395]:variation-location:"exon 3" ;[399..411]:gene-rna:"beta-catenin" ;[458..475]:malignancy:"colorectal tumors" ;[488..514]:gene-rna:"adenomatous polyposis coli" ;[516..519]:gene-rna:"APC" ;[565..577]:gene-rna:"beta-catenin" (SENT (S (S (NP-SBJ-2 (NP (NN:[334..338] Loss)) (PP (IN:[339..341] of) (NP (NP (NP (NN:[342..348] serine) (NML-1 (-NONE-:[348..348] *P*))) (CC:[349..351] or) (NP (NN:[352..361] threonine) (NML-1 (NN:[362..377] phosphorylation) (NNS:[378..383] sites)))) (PP (IN:[384..388] from) (NP (NP (NN:[389..393] exon) (CD:[394..395] 3)) (PP (IN:[396..398] of) (NP (NN:[399..411] beta-catenin)))))))) (VP (VBZ:[413..416] has) (VP (VBN:[417..421] been) (VP (VBN:[422..432] identified) (NP-2 (-NONE-:[432..432] *)) (PP-LOC (IN:[433..435] in) (NP (NP (QP (RB:[436..449] approximately) (NN:[450..454] half))) (PP (IN:[455..457] of) (NP (NP (JJ:[458..468] colorectal) (NNS:[469..475] tumors)) (SBAR (WHNP-3 (WDT:[476..481] which)) (S (NP-SBJ-3 (-NONE-:[481..481] *T*)) (VP (VBP:[482..486] lack) (NP (NML (NML (JJ:[488..499] adenomatous) (NN:[500..509] polyposis) (NN:[510..514] coli)) (NML (-LRB-:[515..516] -LRB-) (NN:[516..519] APC) (-RRB-:[519..520] -RRB-))) (NNS:[521..530] mutations))))))))))))) (,:[530..531] ,) (CC:[532..535] but) (S (NP-SBJ (NP (DT:[536..539] the) (JJ:[540..547] overall) (NN:[548..560] contribution)) (PP (IN:[561..563] of) (NP (NN:[565..577] beta-catenin) (NNS:[578..587] mutations))) (PP (TO:[588..590] to) (NP (JJ:[591..599] sporadic) (JJ:[600..610] colorectal) (NN:[611..624] tumorigenesis)))) (VP (VBZ:[625..627] is) (ADJP-PRD (JJ:[628..635] unclear)))) (.:[635..636] .))) ;sentence 5 Span:637..744 ;We therefore used PCR to amplify and sequence exon 3 of beta-catenin from ;202 sporadic colorectal tumors. ;[684..690]:variation-location:"exon 3" ;[694..706]:gene-rna:"beta-catenin" ;[717..743]:malignancy:"sporadic colorectal tumors" (SENT (S (NP-SBJ (PRP:[637..639] We)) (ADVP (RB:[641..650] therefore)) (VP (VBD:[651..655] used) (NP (NN:[656..659] PCR)) (S-MNR (NP-SBJ (-NONE-:[659..659] *)) (VP (TO:[660..662] to) (VP (VB:[663..670] amplify) (CC:[671..674] and) (VB:[675..683] sequence) (NP (NP (NN:[684..688] exon) (CD:[689..690] 3)) (PP (IN:[691..693] of) (NP (NN:[694..706] beta-catenin))) (PP (IN:[707..711] from) (NP (CD:[712..715] 202) (JJ:[717..725] sporadic) (JJ:[726..736] colorectal) (NNS:[737..743] tumors)))))))) (.:[743..744] .))) ;sentence 6 Span:745..898 ;Exon 3 beta-catenin mutations were identified in 6 of 48 small (< 1 cm) ;adenomas, 2 of 82 large (> or =1 cm) adenomas, and 1 of 72 invasive ;carcinomas. ;[745..751]:variation-location:"Exon 3" ;[752..764]:gene-rna:"beta-catenin" ;[803..808]...[818..826]:malignancy:"small"..."adenomas" ;[836..841]...[855..863]:malignancy:"large"..."adenomas" ;[878..897]:malignancy:"invasive carcinomas" (SENT (S (NP-SBJ-1 (NML (NN:[745..749] Exon) (CD:[750..751] 3)) (NN:[752..764] beta-catenin) (NNS:[765..774] mutations)) (VP (VBD:[775..779] were) (VP (VBN:[780..790] identified) (NP-1 (-NONE-:[790..790] *)) (PP-LOC (IN:[791..793] in) (NP (NP (NP (CD:[794..795] 6)) (PP (IN:[797..799] of) (NP (CD:[800..802] 48) (JJ:[803..808] small) (PRN (-LRB-:[809..810] -LRB-) (NP (QP (SYM:[810..811] <) (CD:[812..813] 1)) (NN:[814..816] cm)) (-RRB-:[816..817] -RRB-)) (NNS:[818..826] adenomas)))) (,:[826..827] ,) (NP (NP (CD:[828..829] 2)) (PP (IN:[830..832] of) (NP (CD:[833..835] 82) (JJ:[836..841] large) (PRN (-LRB-:[842..843] -LRB-) (NP (QP (SYM:[843..844] >) (CC:[845..847] or) (SYM:[848..849] =) (CD:[849..850] 1)) (NN:[851..853] cm)) (-RRB-:[853..854] -RRB-)) (NNS:[855..863] adenomas)))) (,:[863..864] ,) (CC:[865..868] and) (NP (NP (CD:[869..870] 1)) (PP (IN:[871..873] of) (NP (CD:[874..876] 72) (JJ:[878..886] invasive) (NNS:[887..897] carcinomas)))))))) (.:[897..898] .))) ;sentence 7 Span:899..1059 ;Eight of the nine mutations, including all of those in the small adenomas ;and the invasive cancer, involved loss of serine or threonine ;phosphorylation sites. ;[917..926]:variation-event:"mutations" ;[959..973]:malignancy:"small adenomas" ;[982..997]:malignancy:"invasive cancer" (SENT (S (NP-SBJ (NP (CD:[899..904] Eight)) (PP (IN:[905..907] of) (NP (DT:[908..911] the) (CD:[912..916] nine) (NNS:[917..926] mutations))) (,:[926..927] ,) (PP (VBG:[928..937] including) (NP (NP (DT:[938..941] all)) (PP (IN:[942..944] of) (NP (NP (DT:[945..950] those)) (PP (IN:[951..953] in) (NP (NP (DT:[954..957] the) (JJ:[959..964] small) (NNS:[965..973] adenomas)) (CC:[974..977] and) (NP (DT:[978..981] the) (JJ:[982..990] invasive) (NN:[991..997] cancer))))))))) (,:[997..998] ,) (VP (VBD:[999..1007] involved) (NP (NP (NN:[1008..1012] loss)) (PP (IN:[1013..1015] of) (NP (NP (NN:[1016..1022] serine) (NML-1 (-NONE-:[1022..1022] *P*))) (CC:[1023..1025] or) (NP (NN:[1026..1035] threonine) (NML-1 (NN:[1037..1052] phosphorylation) (NNS:[1053..1058] sites))))))) (.:[1058..1059] .))) ;sentence 8 Span:1060..1255 ;The percentage of beta-catenin mutations in small adenomas (12.5%) was ;significantly greater than that in large adenomas (2.4%) and invasive ;cancers (1.4%; P = 0.05 and P = 0.02, respectively). ;[1078..1090]:gene-rna:"beta-catenin" ;[1104..1119]:malignancy:"small adenomas" ;[1167..1181]:malignancy:"large adenomas" ;[1194..1210]:malignancy:"invasive cancers" (SENT (S (NP-SBJ (NP (DT:[1060..1063] The) (NN:[1064..1074] percentage)) (PP (IN:[1075..1077] of) (NP (NN:[1078..1090] beta-catenin) (NNS:[1091..1100] mutations))) (PP-LOC (IN:[1101..1103] in) (NP (JJ:[1104..1109] small) (NNS:[1111..1119] adenomas))) (PRN (-LRB-:[1120..1121] -LRB-) (NP (CD:[1121..1125] 12.5) (NN:[1125..1126] %)) (-RRB-:[1126..1127] -RRB-))) (VP (VBD:[1128..1131] was) (ADJP-PRD (ADJP (RB:[1132..1145] significantly) (JJR:[1146..1153] greater)) (PP (IN:[1154..1158] than) (NP (NP (DT:[1159..1163] that)) (PP-LOC (IN:[1164..1166] in) (NP (NP (JJ:[1167..1172] large) (NNS:[1173..1181] adenomas) (PRN (-LRB-:[1182..1183] -LRB-) (NP (CD:[1183..1186] 2.4) (NN:[1186..1187] %)) (-RRB-:[1187..1188] -RRB-))) (CC:[1190..1193] and) (NP (JJ:[1194..1202] invasive) (NNS:[1203..1210] cancers) (PRN (-LRB-:[1211..1212] -LRB-) (NP (CD:[1212..1215] 1.4) (NN:[1215..1216] %)) (::[1216..1217] ;)))))))) (PRN (S (S (NP-SBJ (NN:[1218..1219] P)) (VP (SYM:[1220..1221] =) (NP (CD:[1222..1226] 0.05)))) (CC:[1227..1230] and) (S (NP-SBJ (NN:[1231..1232] P)) (VP (SYM:[1233..1234] =) (NP (CD:[1235..1239] 0.02)))) (,:[1239..1240] ,) (ADVP (RB:[1241..1253] respectively)) (-RRB-:[1253..1254] -RRB-)))) (.:[1254..1255] .))) ;sentence 9 Span:1256..1371 ;We conclude that mutation of beta-catenin can be an early, perhaps ;initiating, event in colorectal tumorigenesis. ;[1286..1298]:gene-rna:"beta-catenin" (SENT (S (NP-SBJ (PRP:[1256..1258] We)) (VP (VBP:[1259..1267] conclude) (SBAR (IN:[1269..1273] that) (S (NP-SBJ (NP (NN:[1274..1282] mutation)) (PP (IN:[1283..1285] of) (NP (NN:[1286..1298] beta-catenin)))) (VP (MD:[1299..1302] can) (VP (VB:[1303..1305] be) (NP-PRD (DT:[1306..1308] an) (JJ:[1309..1314] early) (,:[1314..1315] ,) (ADJP (RB:[1316..1323] perhaps) (VBG:[1324..1334] initiating)) (,:[1334..1335] ,) (NN:[1336..1341] event)) (PP (IN:[1342..1344] in) (NP (JJ:[1346..1356] colorectal) (NN:[1357..1370] tumorigenesis)))))))) (.:[1370..1371] .))) ;sentence 10 Span:1372..1616 ;Small adenomas with beta-catenin mutations do not appear to be as likely to ;progress to larger adenomas and invasive carcinomas as other adenomas, ;however, with the result that beta-catenin mutations are only rarely seen in ;invasive cancers. ;[1372..1386]:malignancy:"Small adenomas" ;[1392..1404]:gene-rna:"beta-catenin" ;[1461..1476]:malignancy:"larger adenomas" ;[1481..1500]:malignancy:"invasive carcinomas" ;[1511..1519]:malignancy:"adenomas" ;[1551..1563]:gene-rna:"beta-catenin" ;[1599..1615]:malignancy:"invasive cancers" (SENT (S (NP-SBJ-1 (NP (JJ:[1372..1377] Small) (NNS:[1378..1386] adenomas)) (PP (IN:[1387..1391] with) (NP (NN:[1392..1404] beta-catenin) (NNS:[1405..1414] mutations)))) (VP (VBP:[1415..1417] do) (RB:[1418..1421] not) (VP (VB:[1423..1429] appear) (S (NP-SBJ-1 (-NONE-:[1429..1429] *)) (VP (TO:[1430..1432] to) (VP (VB:[1433..1435] be) (ADJP-PRD (ADJP (RB:[1436..1438] as) (JJ:[1439..1445] likely) (S (NP-SBJ (-NONE-:[1445..1445] *)) (VP (TO:[1446..1448] to) (VP (VB:[1449..1457] progress) (PP-CLR (TO:[1458..1460] to) (NP (NP (JJR:[1461..1467] larger) (NNS:[1468..1476] adenomas)) (CC:[1477..1480] and) (NP (JJ:[1481..1489] invasive) (NNS:[1490..1500] carcinomas)))))))) (PP (IN:[1501..1503] as) (NP (JJ:[1505..1510] other) (NNS:[1511..1519] adenomas)))) (,:[1519..1520] ,) (ADVP (RB:[1521..1528] however)) (,:[1528..1529] ,) (PP (IN:[1530..1534] with) (NP (DT:[1535..1538] the) (NN:[1539..1545] result) (SBAR (IN:[1546..1550] that) (S (NP-SBJ-2 (NN:[1551..1563] beta-catenin) (NNS:[1564..1573] mutations)) (VP (VBP:[1574..1577] are) (ADVP (RB:[1578..1582] only) (RB:[1584..1590] rarely)) (VP (VBN:[1591..1595] seen) (NP-2 (-NONE-:[1595..1595] *)) (PP-LOC (IN:[1596..1598] in) (NP (JJ:[1599..1607] invasive) (NNS:[1608..1615] cancers)))))))))))))) (.:[1615..1616] .))) ;sentence 11 Span:1617..1806 ;This suggests that APC and beta-catenin mutations are not functionally ;equivalent, and that the APC gene may have other tumor suppressor functions ;besides the degradation of beta-catenin. ;[1636..1639]:gene-rna:"APC" ;[1644..1656]:gene-rna:"beta-catenin" ;[1714..1717]:gene-rna:"APC" ;[1793..1805]:gene-protein:"beta-catenin" (SENT (S (NP-SBJ (DT:[1617..1621] This)) (VP (VBZ:[1622..1630] suggests) (SBAR (SBAR (IN:[1631..1635] that) (S (NP-SBJ (NP (NN:[1636..1639] APC) (NML-1 (-NONE-:[1639..1639] *P*))) (CC:[1640..1643] and) (NP (NN:[1644..1656] beta-catenin) (NML-1 (NNS:[1658..1667] mutations)))) (VP (VBP:[1668..1671] are) (RB:[1672..1675] not) (ADJP-PRD (RB:[1676..1688] functionally) (JJ:[1689..1699] equivalent))))) (,:[1699..1700] ,) (CC:[1701..1704] and) (SBAR (IN:[1705..1709] that) (S (NP-SBJ (DT:[1710..1713] the) (NN:[1714..1717] APC) (NN:[1718..1722] gene)) (VP (MD:[1723..1726] may) (VP (VB:[1727..1731] have) (NP (NP (JJ:[1732..1737] other) (NML (NN:[1739..1744] tumor) (NN:[1745..1755] suppressor)) (NNS:[1756..1765] functions)) (PP (IN:[1766..1773] besides) (NP (NP (DT:[1774..1777] the) (NN:[1778..1789] degradation)) (PP (IN:[1790..1792] of) (NP (NN:[1793..1805] beta-catenin)))))))))))) (.:[1805..1806] .))) ;section 12 Span:1810..1855 ;PMID: 10197610 [PubMed - indexed for MEDLINE] (SEC (FRAG (NNP:[1810..1814] PMID) (::[1814..1815] :) (CD:[1816..1824] 10197610) (NN:[1825..1826] -LSB-) (NNP:[1826..1832] PubMed) (::[1833..1834] -) (NN:[1835..1842] indexed) (IN:[1843..1846] for) (NNP:[1847..1855] MEDLINE-RSB-)))