;PMID: 10213482 ;source_file_1303.mrg ;Release 0.9 of PennBioIE ;Funded by NSF ITR EIA-0205448 ;0)section:[e:0..36] = [t:0..36] ;1)sentence:[e:41..133] = [t:41..133] ;2)section:[e:137..211] = [t:137..211] ;3)section:[e:215..334] = [t:215..334] ;4)sentence:[e:338..536] = [t:338..536] ;5)sentence:[e:537..749] = [t:537..749] ;6)sentence:[e:750..895] = [t:750..895] ;7)sentence:[e:896..1170] = [t:896..1170] ;8)sentence:[e:1172..1267] = [t:1172..1267] ;9)sentence:[e:1268..1434] = [t:1268..1434] ;10)sentence:[e:1435..1625] = [t:1435..1625] ;11)sentence:[e:1627..1762] = [t:1627..1762] ;12)section:[e:1766..1811] = [t:1766..1811] ;section 0 Span:0..36 ;Cancer Res 1999 Apr 15;59(8):1811-5 (SEC (FRAG (NN:[0..6] Cancer) (NNP:[7..10] Res) (CD:[12..16] 1999) (NNP:[17..20] Apr) (CD:[21..23] 15) (CD:[23..25] ;5) (CD:[25..26] 9) (NN:[26..27] -LRB-) (NN:[27..28] 8) (NN:[28..29] -RRB-) (::[29..30] :) (CD:[30..34] 1811) (::[34..36] -5))) ;sentence 1 Span:41..133 ;Frequent mutation and nuclear localization of beta-catenin in anaplastic ;thyroid carcinoma. ;[50..58]:variation-event:"mutation" ;[87..99]:gene-protein:"beta-catenin" ;[114..132]:malignancy-type:"thyroid carcinoma" (SENT (NP-HLN (NP (NP (JJ:[41..49] Frequent) (NN:[50..58] mutation)) (CC:[59..62] and) (NP (JJ:[63..70] nuclear) (NN:[71..83] localization))) (PP (IN:[84..86] of) (NP (NN:[87..99] beta-catenin))) (PP (IN:[100..102] in) (NP (JJ:[103..113] anaplastic) (NN:[114..121] thyroid) (NN:[123..132] carcinoma))) (.:[132..133] .))) ;section 2 Span:137..211 ;Garcia-Rostan G, Tallini G, Herrero A, D'Aquila TG, Carcangiu ML, Rimm DL. (SEC (FRAG (NNP:[137..150] Garcia-Rostan) (NNP:[151..152] G) (,:[152..153] ,) (NNP:[154..161] Tallini) (NNP:[162..163] G) (,:[163..164] ,) (NNP:[165..172] Herrero) (NNP:[173..174] A) (,:[174..175] ,) (NNP:[176..184] D'Aquila) (NNP:[185..187] TG) (,:[187..188] ,) (NNP:[189..198] Carcangiu) (NNP:[199..201] ML) (,:[201..202] ,) (NNP:[203..207] Rimm) (NNP:[208..211] DL.))) ;section 3 Span:215..334 ;Department of Pathology, Yale University School of Medicine, New Haven, ;Connecticut 06520, USA. ginesa.rostan@yale.edu (SEC (FRAG (NNP:[215..225] Department) (IN:[226..228] of) (NNP:[229..238] Pathology) (,:[238..239] ,) (NNP:[240..244] Yale) (NNP:[245..255] University) (NNP:[256..262] School) (IN:[263..265] of) (NNP:[266..274] Medicine) (,:[274..275] ,) (NNP:[276..279] New) (NNP:[280..285] Haven) (,:[285..286] ,) (NNP:[288..299] Connecticut) (CD:[300..305] 06520) (,:[305..306] ,) (NNP:[307..310] USA) (.:[310..311] .) (IN:[312..330] ginesa.rostan@yale) (NN:[330..334] .edu))) ;sentence 4 Span:338..536 ;Beta-catenin is an ubiquitously expressed cytoplasmic protein that has a ;crucial role in both E-cadherin-mediated cell-cell adhesion and as a ;downstream signaling molecule in the wingless pathway. ;[338..350]:gene-protein:"Beta-catenin" ;[433..443]:gene-protein:"E-cadherin" ;[519..527]:gene-generic:"wingless" (SENT (S (NP-SBJ (NN:[338..350] Beta-catenin)) (VP (VBZ:[351..353] is) (NP-PRD (NP (DT:[354..356] an) (ADJP (RB:[357..369] ubiquitously) (VBN:[370..379] expressed)) (JJ:[380..391] cytoplasmic) (NN:[392..399] protein)) (SBAR (WHNP-1 (WDT:[400..404] that)) (S (NP-SBJ-1 (-NONE-:[404..404] *T*)) (VP (VBZ:[405..408] has) (NP (NP (DT:[409..410] a) (JJ:[411..418] crucial) (NN:[420..424] role)) (PP (PP (IN:[425..427] in) (NP (CC:[428..432] both) (ADJP (NN:[433..443] E-cadherin) (HYPH:[443..444] -) (VBN:[444..452] mediated)) (NML (NML (NN:[453..457] cell)) (PP (HYPH:[457..458] -) (NP (NN:[458..462] cell)))) (NN:[463..471] adhesion))) (CC:[472..475] and) (PP (IN:[476..478] as) (NP (DT:[479..480] a) (JJ:[481..491] downstream) (VBG:[493..502] signaling) (NN:[503..511] molecule)))) (PP (IN:[512..514] in) (NP (DT:[515..518] the) (JJ:[519..527] wingless) (NN:[528..535] pathway))))))))) (.:[535..536] .))) ;sentence 5 Span:537..749 ;Stabilization of beta-catenin followed by nuclear translocation and ;subsequent T-cell factor/lymphoid-enhancing factor-mediated transcriptional ;activation has been proposed as an important step in oncogenesis. ;[554..566]:gene-protein:"beta-catenin" ;[617..631]:gene-protein:"T-cell factor" ;[632..657]:gene-protein:"lymphoid-enhancing factor" (SENT (S (NP-SBJ-1 (NP (NP (NN:[537..550] Stabilization)) (PP (IN:[551..553] of) (NP (NN:[554..566] beta-catenin)))) (VP (VBN:[568..576] followed) (NP (-NONE-:[576..576] *)) (PP (IN:[577..579] by) (NP-LGS (NP (JJ:[580..587] nuclear) (NN:[588..601] translocation)) (CC:[602..605] and) (NP (JJ:[606..616] subsequent) (ADJP (NML (NML (NN:[617..623] T-cell) (NN:[625..631] factor)) (SYM:[631..632] /) (NML (JJ:[632..640] lymphoid) (HYPH:[640..641] -) (VBG:[641..650] enhancing) (NN:[651..657] factor))) (HYPH:[657..658] -) (VBN:[658..666] mediated)) (JJ:[667..682] transcriptional) (NN:[683..693] activation)))))) (VP (VBZ:[694..697] has) (VP (VBN:[698..702] been) (VP (VBN:[704..712] proposed) (NP-1 (-NONE-:[712..712] *)) (PP (IN:[713..715] as) (NP (NP (DT:[716..718] an) (JJ:[719..728] important) (NN:[729..733] step)) (PP (IN:[734..736] in) (NP (NN:[737..748] oncogenesis)))))))) (.:[748..749] .))) ;sentence 6 Span:750..895 ;Stabilization may occur through activating mutations in exon-3 at the ;phosphorylation sites for ubiquitination and degradation of beta-catenin. ;[794..803]:variation-event:"mutations" ;[807..813]:variation-location:"exon-3" ;[882..894]:gene-protein:"beta-catenin" (SENT (S (NP-SBJ (NN:[750..763] Stabilization)) (VP (MD:[764..767] may) (VP (VB:[768..773] occur) (PP (IN:[774..781] through) (NP (NP (VBG:[783..793] activating) (NNS:[794..803] mutations)) (PP (IN:[804..806] in) (NP (NN:[807..813] exon-3))))) (PP-LOC (IN:[814..816] at) (NP (NP (DT:[817..820] the) (NN:[821..836] phosphorylation) (NNS:[837..842] sites)) (PP (IN:[843..846] for) (NP (NP (NN:[847..861] ubiquitination) (CC:[863..866] and) (NN:[867..878] degradation)) (PP (IN:[879..881] of) (NP (NN:[882..894] beta-catenin))))))))) (.:[894..895] .))) ;sentence 7 Span:896..1170 ;Immunohistochemical subcellular localization of beta-catenin and mutational ;analysis of exon-3 of the beta-catenin gene by single-strand conformational ;polymorphism followed by DNA sequencing was performed on 37 samples from 31 ;patients with anaplastic thyroid carcinoma. ;[945..957]:gene-protein:"beta-catenin" ;[985..991]:variation-location:"exon-3" ;[999..1011]:gene-rna:"beta-catenin" ;[1152..1169]:malignancy-type:"thyroid carcinoma" (SENT (S (NP-SBJ-1 (NP (NP (JJ:[896..915] Immunohistochemical) (JJ:[916..927] subcellular) (NN:[928..940] localization)) (PP (IN:[941..943] of) (NP (NN:[945..957] beta-catenin)))) (CC:[958..961] and) (NP (NP (JJ:[962..972] mutational) (NN:[973..981] analysis)) (PP (IN:[982..984] of) (NP (NP (NN:[985..991] exon-3)) (PP (IN:[992..994] of) (NP (DT:[995..998] the) (NN:[999..1011] beta-catenin) (NN:[1012..1016] gene))))) (PP (IN:[1017..1019] by) (NP (NP (NML (JJ:[1021..1027] single) (HYPH:[1027..1028] -) (NN:[1028..1034] strand)) (JJ:[1035..1049] conformational) (NN:[1050..1062] polymorphism)) (VP (VBN:[1063..1071] followed) (NP (-NONE-:[1071..1071] *)) (PP (IN:[1072..1074] by) (NP-LGS (NN:[1075..1078] DNA) (NN:[1079..1089] sequencing)))))))) (VP (VBD:[1090..1093] was) (VP (VBN:[1095..1104] performed) (NP-1 (-NONE-:[1104..1104] *)) (PP (IN:[1105..1107] on) (NP (NP (CD:[1108..1110] 37) (NNS:[1111..1118] samples)) (PP (IN:[1119..1123] from) (NP (NP (CD:[1124..1126] 31) (NNS:[1127..1135] patients)) (PP (IN:[1136..1140] with) (NP (JJ:[1141..1151] anaplastic) (NN:[1152..1159] thyroid) (NN:[1160..1169] carcinoma))))))))) (.:[1169..1170] .))) ;sentence 8 Span:1172..1267 ;Immunofluorescent staining showed nuclear localization in 15 (42%) of the 36 ;samples examined. (SENT (S (NP-SBJ (JJ:[1172..1189] Immunofluorescent) (NN:[1190..1198] staining)) (VP (VBD:[1199..1205] showed) (NP (JJ:[1206..1213] nuclear) (NN:[1214..1226] localization)) (PP (IN:[1227..1229] in) (NP (NP (CD:[1230..1232] 15) (PRN (-LRB-:[1233..1234] -LRB-) (NP (CD:[1234..1236] 42) (NN:[1236..1237] %)) (-RRB-:[1237..1238] -RRB-))) (PP (IN:[1239..1241] of) (NP (NP (DT:[1242..1245] the) (CD:[1246..1248] 36) (NNS:[1250..1257] samples)) (VP (VBN:[1258..1266] examined) (NP (-NONE-:[1266..1266] *)))))))) (.:[1266..1267] .))) ;sentence 9 Span:1268..1434 ;Nucleotide sequencing of mobility shifts detected by single-strand ;conformational polymorphism revealed somatic alterations in 19 (61%) of the ;31 patients analyzed. (SENT (S (NP-SBJ (NP (NN:[1268..1278] Nucleotide) (NN:[1279..1289] sequencing)) (PP (IN:[1290..1292] of) (NP (NP (NN:[1293..1301] mobility) (NNS:[1302..1308] shifts)) (VP (VBN:[1309..1317] detected) (NP (-NONE-:[1317..1317] *)) (PP-MNR (IN:[1318..1320] by) (NP (NML (JJ:[1322..1328] single) (HYPH:[1328..1329] -) (NN:[1329..1335] strand)) (JJ:[1336..1350] conformational) (NN:[1351..1363] polymorphism))))))) (VP (VBD:[1364..1372] revealed) (NP (NP (JJ:[1373..1380] somatic) (NNS:[1381..1392] alterations)) (PP (IN:[1393..1395] in) (NP (NP (CD:[1396..1398] 19) (PRN (-LRB-:[1400..1401] -LRB-) (NP (CD:[1401..1403] 61) (NN:[1403..1404] %)) (-RRB-:[1404..1405] -RRB-))) (PP (IN:[1406..1408] of) (NP (NP (DT:[1409..1412] the) (CD:[1413..1415] 31) (NNS:[1416..1424] patients)) (VP (VBN:[1425..1433] analyzed) (NP (-NONE-:[1433..1433] *))))))))) (.:[1433..1434] .))) ;sentence 10 Span:1435..1625 ;We conclude that mutations in beta-catenin are common in anaplastic thyroid ;cancer and that they may activate transcription, as illustrated by frequent ;nuclear localization of the protein. ;[1465..1477]:gene-rna:"beta-catenin" ;[1504..1518]:malignancy-type:"thyroid cancer" (SENT (S (NP-SBJ (PRP:[1435..1437] We)) (VP (VBP:[1438..1446] conclude) (SBAR (SBAR (IN:[1447..1451] that) (S (NP-SBJ (NP (NNS:[1452..1461] mutations)) (PP (IN:[1462..1464] in) (NP (NN:[1465..1477] beta-catenin)))) (VP (VBP:[1479..1482] are) (ADJP-PRD (JJ:[1483..1489] common)) (PP (IN:[1490..1492] in) (NP (JJ:[1493..1503] anaplastic) (NN:[1504..1511] thyroid) (NN:[1512..1518] cancer)))))) (CC:[1519..1522] and) (SBAR (IN:[1523..1527] that) (S (NP-SBJ (PRP:[1528..1532] they)) (VP (MD:[1533..1536] may) (VP (VB:[1537..1545] activate) (NP (NN:[1547..1560] transcription)) (,:[1560..1561] ,) (SBAR (IN:[1562..1564] as) (S (NP-SBJ-1 (-NONE-:[1564..1564] *)) (VP (VBN:[1565..1576] illustrated) (NP-1 (-NONE-:[1576..1576] *)) (PP (IN:[1577..1579] by) (NP (NP (JJ:[1580..1588] frequent) (JJ:[1589..1596] nuclear) (NN:[1597..1609] localization)) (PP (IN:[1610..1612] of) (NP (DT:[1613..1616] the) (NN:[1617..1624] protein)))))))))))))) (.:[1624..1625] .))) ;sentence 11 Span:1627..1762 ;These findings support the idea that beta-catenin acts as an oncogene and ;contributes to the highly aggressive behavior of this tumor. ;[1664..1676]:gene-rna:"beta-catenin" (SENT (S (NP-SBJ (DT:[1627..1632] These) (NNS:[1633..1641] findings)) (VP (VBP:[1642..1649] support) (NP (DT:[1650..1653] the) (NN:[1654..1658] idea) (SBAR (IN:[1659..1663] that) (S (NP-SBJ (NN:[1664..1676] beta-catenin)) (VP (VP (VBZ:[1677..1681] acts) (PP (IN:[1682..1684] as) (NP (DT:[1685..1687] an) (NN:[1688..1696] oncogene)))) (CC:[1697..1700] and) (VP (VBZ:[1702..1713] contributes) (PP (TO:[1714..1716] to) (NP (NP (DT:[1717..1720] the) (ADJP (RB:[1721..1727] highly) (JJ:[1728..1738] aggressive)) (NN:[1739..1747] behavior)) (PP (IN:[1748..1750] of) (NP (DT:[1751..1755] this) (NN:[1756..1761] tumor))))))))))) (.:[1761..1762] .))) ;section 12 Span:1766..1811 ;PMID: 10213482 [PubMed - indexed for MEDLINE] (SEC (FRAG (NNP:[1766..1770] PMID) (::[1770..1771] :) (CD:[1772..1780] 10213482) (NN:[1781..1782] -LSB-) (NNP:[1782..1788] PubMed) (::[1789..1790] -) (NN:[1791..1798] indexed) (IN:[1799..1802] for) (NNP:[1803..1811] MEDLINE-RSB-)))