;PMID: 9927029 ;source_file_1368.mrg ;Release 0.9 of PennBioIE ;Funded by NSF ITR EIA-0205448 ;0)section:[e:0..36] = [t:0..36] ;1)sentence:[e:41..146] = [t:41..146] ;2)section:[e:150..223] = [t:150..223] ;3)section:[e:227..300] = [t:227..300] ;4)sentence:[e:304..444] = [t:304..444] ;5)sentence:[e:445..500] = [t:445..500] ;6)sentence:[e:501..623] = [t:501..623] ;7)sentence:[e:624..698] = [t:624..698] ;8)sentence:[e:699..835] = [t:699..835] ;9)sentence:[e:836..973] = [t:836..973] ;10)sentence:[e:974..1165] = [t:974..1165] ;11)sentence:[e:1166..1350] = [t:1166..1350] ;12)sentence:[e:1351..1515] = [t:1351..1515] ;13)sentence:[e:1516..1640] = [t:1516..1640] ;14)section:[e:1644..1688] = [t:1644..1688] ;section 0 Span:0..36 ;Cancer Res 1999 Jan 15;59(2):269-73 (SEC (FRAG (NN:[0..6] Cancer) (NNP:[7..10] Res) (CD:[12..16] 1999) (NNP:[17..20] Jan) (CD:[21..27] 15;59-LRB-) (CD:[27..28] 2) (-RRB-:[28..29] -RRB-) (CD:[29..33] :269) (IN:[33..34] -) (CD:[34..36] 73))) ;sentence 1 Span:41..146 ;Childhood hepatoblastomas frequently carry a mutated degradation targeting ;box of the beta-catenin gene. ;[41..66]:malignancy:"Childhood hepatoblastomas" ;[128..140]:gene-rna:"beta-catenin" (SENT (S-HLN (NP-SBJ (NN:[41..50] Childhood) (NNS:[51..66] hepatoblastomas)) (ADVP (RB:[67..77] frequently)) (VP (VBP:[78..83] carry) (NP (NP (DT:[84..85] a) (VBN:[86..93] mutated) (NN:[94..105] degradation) (VBG:[106..115] targeting) (NN:[116..119] box)) (PP (IN:[121..123] of) (NP (DT:[124..127] the) (NN:[128..140] beta-catenin) (NN:[141..145] gene))))) (.:[145..146] .))) ;section 2 Span:150..223 ;Koch A, Denkhaus D, Albrecht S, Leuschner I, von Schweinitz D, Pietsch T. (SEC (FRAG (NNP:[150..154] Koch) (NNP:[155..156] A) (,:[156..157] ,) (NNP:[158..166] Denkhaus) (NNP:[167..168] D) (,:[168..169] ,) (NNP:[170..178] Albrecht) (NNP:[179..181] S,) (NNP:[182..191] Leuschner) (NNP:[192..193] I) (,:[193..194] ,) (NNP:[195..198] von) (NNP:[199..209] Schweinitz) (NNP:[210..211] D) (,:[211..212] ,) (NNP:[213..220] Pietsch) (NNP:[221..223] T.))) ;section 3 Span:227..300 ;Department of Neuropathology, University of Bonn Medical Center, Germany. (SEC (FRAG (NNP:[227..237] Department) (IN:[238..240] of) (NNP:[241..255] Neuropathology) (,:[255..256] ,) (NNP:[257..267] University) (IN:[268..270] of) (NNP:[271..275] Bonn) (NNP:[276..283] Medical) (NNP:[284..290] Center) (,:[290..291] ,) (NNP:[292..299] Germany) (.:[299..300] .))) ;sentence 4 Span:304..444 ;Hepatoblastomas (HBs) are embryonal tumors affecting young children and ;representing the most frequent malignant liver tumors in childhood. ;[304..319]:malignancy:"Hepatoblastomas" ;[321..324]:malignancy:"HBs" ;[330..346]:malignancy:"embryonal tumors" ;[408..443]:malignancy:"malignant liver tumors in childhood" (SENT (S (NP-SBJ (NP (NNS:[304..319] Hepatoblastomas)) (NP (-LRB-:[320..321] -LRB-) (NNS:[321..324] HBs) (-RRB-:[324..325] -RRB-))) (VP (VBP:[326..329] are) (NP-PRD (NP (JJ:[330..339] embryonal) (NNS:[340..346] tumors)) (VP (VP (VBG:[347..356] affecting) (NP (JJ:[357..362] young) (NNS:[363..371] children))) (CC:[372..375] and) (VP (VBG:[377..389] representing) (NP (DT:[390..393] the) (ADJP (RBS:[394..398] most) (JJ:[399..407] frequent)) (JJ:[408..417] malignant) (NN:[418..423] liver) (NNS:[424..430] tumors)) (PP (IN:[431..433] in) (NP (NN:[434..443] childhood))))))) (.:[443..444] .))) ;sentence 5 Span:445..500 ;The molecular pathogenesis of HB is poorly understood. ;[476..478]:malignancy:"HB" (SENT (S (NP-SBJ-1 (NP (DT:[445..448] The) (JJ:[450..459] molecular) (NN:[460..472] pathogenesis)) (PP (IN:[473..475] of) (NP (NN:[476..478] HB)))) (VP (VBZ:[479..481] is) (ADVP (RB:[482..488] poorly)) (VP (VBN:[489..499] understood) (NP-1 (-NONE-:[499..499] *)))) (.:[499..500] .))) ;sentence 6 Span:501..623 ;Although most cases are sporadic, the incidence is highly elevated in ;patients with familial adenomatous polyposis coli. ;[586..622]:malignancy:"familial adenomatous polyposis coli" (SENT (S (SBAR-ADV (IN:[501..509] Although) (S (NP-SBJ (JJS:[510..514] most) (NNS:[515..520] cases)) (VP (VBP:[521..524] are) (ADJP-PRD (JJ:[526..534] sporadic))))) (,:[534..535] ,) (NP-SBJ-1 (DT:[536..539] the) (NN:[540..549] incidence)) (VP (VBZ:[550..552] is) (ADVP (RB:[553..559] highly)) (VP (VBN:[560..568] elevated) (NP-1 (-NONE-:[568..568] *)) (PP-LOC (IN:[569..571] in) (NP (NP (NNS:[572..580] patients)) (PP (IN:[581..585] with) (NP (JJ:[586..594] familial) (JJ:[595..606] adenomatous) (NN:[608..617] polyposis) (NN:[618..622] coli))))))) (.:[622..623] .))) ;sentence 7 Span:624..698 ;These patients carry germline mutations of the APC tumor suppressor gene. ;[671..674]:gene-rna:"APC" (SENT (S (NP-SBJ (DT:[624..629] These) (NNS:[630..638] patients)) (VP (VBP:[639..644] carry) (NP (NP (NN:[645..653] germline) (NNS:[654..663] mutations)) (PP (IN:[664..666] of) (NP (DT:[667..670] the) (NN:[671..674] APC) (NML (NN:[675..680] tumor) (NN:[682..692] suppressor)) (NN:[693..697] gene))))) (.:[697..698] .))) ;sentence 8 Span:699..835 ;APC controls the degradation of the oncogene product beta-catenin after its ;NH2-terminal phosphorylation on serine/threonine residues. ;[699..702]:gene-rna:"APC" ;[753..765]:gene-protein:"beta-catenin" (SENT (S (NP-SBJ (NN:[699..702] APC)) (VP (VBZ:[703..711] controls) (NP (NP (DT:[712..715] the) (NN:[716..727] degradation)) (PP (IN:[728..730] of) (NP (NP (DT:[731..734] the) (NN:[735..743] oncogene) (NN:[744..751] product)) (NP (NN:[753..765] beta-catenin))))) (PP-TMP (IN:[766..771] after) (NP (NP (PRP$:[772..775] its) (NML (NN:[776..779] NH2) (HYPH:[779..780] -) (JJ:[780..788] terminal)) (NN:[789..804] phosphorylation)) (PP (IN:[805..807] on) (NP (NML (NN:[808..814] serine) (SYM:[814..815] /) (NN:[815..824] threonine)) (NNS:[826..834] residues)))))) (.:[834..835] .))) ;sentence 9 Span:836..973 ;APC, as well as beta-catenin, has been found to be a central effector of the ;growth promoting wingless signaling pathway in development. ;[836..839]:gene-rna:"APC" ;[852..864]:gene-protein:"beta-catenin" ;[931..939]:gene-rna:"wingless" (SENT (S (NP-SBJ-1 (NP (NN:[836..839] APC)) (,:[839..840] ,) (CONJP (RB:[841..843] as) (RB:[844..848] well) (IN:[849..851] as)) (NP (NN:[852..864] beta-catenin))) (,:[864..865] ,) (VP (VBZ:[866..869] has) (VP (VBN:[870..874] been) (VP (VBN:[875..880] found) (S (NP-SBJ-1 (-NONE-:[880..880] *)) (VP (TO:[881..883] to) (VP (VB:[884..886] be) (NP-PRD (NP (DT:[887..888] a) (JJ:[889..896] central) (NN:[897..905] effector)) (PP (IN:[907..909] of) (NP (DT:[910..913] the) (ADJP (NN:[914..920] growth) (VBG:[921..930] promoting)) (ADJP (JJ:[931..939] wingless) (VBG:[940..949] signaling)) (NN:[950..957] pathway)))) (PP (IN:[958..960] in) (NP (NN:[961..972] development))))))))) (.:[972..973] .))) ;sentence 10 Span:974..1165 ;To find out if this pathway is involved in the pathogenesis of sporadic HBs, ;we examined 52 biopsies and three cell lines from sporadic HBs for mutations ;in the APC and beta-catenin genes. ;[1038..1050]:malignancy:"sporadic HBs" ;[1103..1115]:malignancy:"sporadic HBs" ;[1137..1140]:gene-rna:"APC" ;[1146..1158]:gene-rna:"beta-catenin" (SENT (S (S-PRP (NP-SBJ (-NONE-:[974..974] *)) (VP (TO:[974..976] To) (VP (VB:[977..981] find) (PRT (RP:[982..985] out)) (SBAR (IN:[987..989] if) (S (NP-SBJ-2 (DT:[990..994] this) (NN:[995..1002] pathway)) (VP (VBZ:[1003..1005] is) (VP (VBN:[1006..1014] involved) (NP-2 (-NONE-:[1014..1014] *)) (PP-CLR (IN:[1015..1017] in) (NP (NP (DT:[1018..1021] the) (NN:[1022..1034] pathogenesis)) (PP (IN:[1035..1037] of) (NP (JJ:[1038..1046] sporadic) (NNS:[1047..1050] HBs)))))))))))) (,:[1050..1051] ,) (NP-SBJ (PRP:[1052..1054] we)) (VP (VBD:[1055..1063] examined) (NP (NP (CD:[1064..1066] 52) (NNS:[1068..1076] biopsies)) (CC:[1077..1080] and) (NP (NP (CD:[1081..1086] three) (NN:[1087..1091] cell) (NNS:[1092..1097] lines)) (PP (IN:[1098..1102] from) (NP (JJ:[1103..1111] sporadic) (NNS:[1112..1115] HBs))))) (PP (IN:[1116..1119] for) (NP (NP (NNS:[1120..1129] mutations)) (PP-LOC (IN:[1130..1132] in) (NP (DT:[1133..1136] the) (NML (NML (NN:[1137..1140] APC) (NML-1 (-NONE-:[1140..1140] *P*))) (CC:[1141..1144] and) (NML (NN:[1146..1158] beta-catenin) (NML-1 (NNS:[1159..1164] genes))))))))) (.:[1164..1165] .))) ;sentence 11 Span:1166..1350 ;Using single-strand conformational polymorphism analysis, deletion screening ;by PCR, and direct sequencing, we found a high frequency of beta-catenin ;mutations in sporadic HBs (48%). ;[1305..1317]:gene-rna:"beta-catenin" ;[1331..1343]:malignancy:"sporadic HBs" (SENT (S (S-MNR (NP-SBJ (-NONE-:[1166..1166] *)) (VP (VBG:[1166..1171] Using) (NP (NP (NML (JJ:[1172..1178] single) (HYPH:[1178..1179] -) (NN:[1179..1185] strand)) (JJ:[1186..1200] conformational) (NN:[1201..1213] polymorphism) (NN:[1214..1222] analysis)) (,:[1222..1223] ,) (NP (NP (NN:[1225..1233] deletion) (NN:[1234..1243] screening)) (PP (IN:[1244..1246] by) (NP (NN:[1247..1250] PCR)))) (,:[1250..1251] ,) (CC:[1252..1255] and) (NP (JJ:[1256..1262] direct) (NN:[1263..1273] sequencing))))) (,:[1273..1274] ,) (NP-SBJ (PRP:[1275..1277] we)) (VP (VBD:[1278..1283] found) (NP (NP (DT:[1284..1285] a) (JJ:[1286..1290] high) (NN:[1291..1300] frequency)) (PP (IN:[1301..1303] of) (NP (NN:[1305..1317] beta-catenin) (NNS:[1318..1327] mutations)))) (PP (IN:[1328..1330] in) (NP (JJ:[1331..1339] sporadic) (NNS:[1340..1343] HBs))) (PRN (-LRB-:[1344..1345] -LRB-) (NP (CD:[1345..1347] 48) (NN:[1347..1348] %)) (-RRB-:[1348..1349] -RRB-))) (.:[1349..1350] .))) ;sentence 12 Span:1351..1515 ;The mutations affected exon 3 encoding the degradation targeting box of ;beta-catenin leading to accumulation of intracytoplasmic and nuclear ;beta-catenin protein. ;[1355..1364]:variation-event:"mutations" ;[1374..1380]:variation-location:"exon 3" ;[1424..1436]:gene-rna:"beta-catenin" ;[1494..1506]:gene-protein:"beta-catenin" (SENT (S (NP-SBJ (DT:[1351..1354] The) (NNS:[1355..1364] mutations)) (VP (VBD:[1365..1373] affected) (NP (NP (NN:[1374..1378] exon) (CD:[1379..1380] 3)) (VP (VBG:[1382..1390] encoding) (NP (NP (DT:[1391..1394] the) (NN:[1395..1406] degradation) (VBG:[1407..1416] targeting) (NN:[1417..1420] box)) (PP (IN:[1421..1423] of) (NP (NN:[1424..1436] beta-catenin)))))) (S-ADV (NP-SBJ (-NONE-:[1436..1436] *)) (VP (VBG:[1437..1444] leading) (PP-CLR (TO:[1445..1447] to) (NP (NP (NN:[1448..1460] accumulation)) (PP (IN:[1462..1464] of) (NP (NP (JJ:[1465..1481] intracytoplasmic) (NML-1 (-NONE-:[1481..1481] *P*))) (CC:[1482..1485] and) (NP (JJ:[1486..1493] nuclear) (NML-1 (NN:[1494..1506] beta-catenin) (NN:[1507..1514] protein)))))))))) (.:[1514..1515] .))) ;sentence 13 Span:1516..1640 ;The high frequency of activating mutations in the beta-catenin gene ;indicates an important role in the pathogenesis of HB. ;[1567..1579]:gene-rna:"beta-catenin" ;[1637..1639]:malignancy:"HB" (SENT (S (NP-SBJ (NP (DT:[1516..1519] The) (JJ:[1520..1524] high) (NN:[1525..1534] frequency)) (PP (IN:[1535..1537] of) (NP (NP (VBG:[1539..1549] activating) (NNS:[1550..1559] mutations)) (PP (IN:[1560..1562] in) (NP (DT:[1563..1566] the) (NN:[1567..1579] beta-catenin) (NN:[1580..1584] gene)))))) (VP (VBZ:[1585..1594] indicates) (NP (DT:[1595..1597] an) (JJ:[1598..1607] important) (NN:[1608..1612] role)) (PP (IN:[1613..1615] in) (NP (NP (DT:[1616..1619] the) (NN:[1621..1633] pathogenesis)) (PP (IN:[1634..1636] of) (NP (NN:[1637..1639] HB)))))) (.:[1639..1640] .))) ;section 14 Span:1644..1688 ;PMID: 9927029 [PubMed - indexed for MEDLINE] (SEC (FRAG (NNP:[1644..1648] PMID) (::[1648..1649] :) (CD:[1650..1657] 9927029) (-LRB-:[1658..1659] -LSB-) (NNP:[1659..1665] PubMed) (HYPH:[1666..1667] -) (NN:[1668..1675] indexed) (IN:[1676..1679] for) (NNP:[1680..1687] MEDLINE) (-RRB-:[1687..1688] -RSB-)))