;PMID: 10936679 ;source_file_1357.mrg ;Release 0.9 of PennBioIE ;Funded by NSF ITR EIA-0205448 ;0)section:[e:0..37] = [t:0..37] ;1)sentence:[e:42..172] = [t:42..172] ;2)section:[e:176..226] = [t:176..226] ;3)section:[e:230..373] = [t:230..373] ;4)sentence:[e:377..623] = [t:377..623] ;5)sentence:[e:624..751] = [t:624..751] ;6)sentence:[e:752..859] = [t:752..859] ;7)sentence:[e:860..993] = [t:860..993] ;8)sentence:[e:994..1205] = [t:994..1205] ;9)sentence:[e:1206..1367] = [t:1206..1367] ;10)section:[e:1371..1416] = [t:1371..1416] ;section 0 Span:0..37 ;Cancer Lett 2000 Sep 1;157(2):185-91 (SEC (FRAG (NN:[0..6] Cancer) (NNP:[7..11] Lett) (CD:[13..17] 2000) (NNP:[18..21] Sep) (CD:[22..28] 1;157-LRB-) (CD:[28..29] 2) (-RRB-:[29..30] -RRB-) (CD:[30..34] :185) (HYPH:[34..35] -) (CD:[35..37] 91))) ;sentence 1 Span:42..172 ;Beta-catenin and adenomatous polyposis coli (APC) mutations in adenomas from ;hereditary non-polyposis colorectal cancer patients. ;[42..54]:gene-rna:"Beta-catenin" ;[59..85]:gene-rna:"adenomatous polyposis coli" ;[87..90]:gene-rna:"APC" ;[105..113]:malignancy:"adenomas" ;[120..162]:malignancy:"hereditary non-polyposis colorectal cancer" (SENT (NP (NP (NP (NN:[42..54] Beta-catenin) (NML-1 (-NONE-:[54..54] *P*))) (CC:[55..58] and) (NP (NML (NML (JJ:[59..70] adenomatous) (NN:[71..80] polyposis) (NN:[81..85] coli)) (NML (-LRB-:[86..87] -LRB-) (NN:[87..90] APC) (-RRB-:[90..91] -RRB-))) (NML-1 (NNS:[92..101] mutations)))) (PP (IN:[102..104] in) (NP (NP (NNS:[105..113] adenomas)) (PP (IN:[114..118] from) (NP (JJ:[120..130] hereditary) (NML (AFX:[131..134] non) (HYPH:[134..135] -) (NN:[135..144] polyposis)) (JJ:[145..155] colorectal) (NN:[156..162] cancer) (NNS:[163..171] patients))))) (.:[171..172] .))) ;section 2 Span:176..226 ;Akiyama Y, Nagasaki H, Yagi KO, Nomizu T, Yuasa Y. (SEC (FRAG (NNP:[176..183] Akiyama) (NNP:[184..185] Y) (,:[185..186] ,) (NNP:[187..195] Nagasaki) (NNP:[196..197] H) (,:[197..198] ,) (NNP:[199..203] Yagi) (NNP:[204..206] KO) (VBD:[206..207] ,) (NNP:[208..214] Nomizu) (NNP:[215..216] T) (,:[216..217] ,) (NNP:[218..223] Yuasa) (NNP:[224..226] Y.))) ;section 3 Span:230..373 ;Department of Hygiene and Oncology, Tokyo Medical and Dental University ;School of Medicine, 1-5-45 Yushima, Bunkyo-ku, 113-8519, Tokyo, Japan. (SEC (FRAG (NNP:[230..240] Department) (IN:[241..243] of) (NNP:[244..251] Hygiene) (CC:[252..255] and) (NNP:[256..264] Oncology) (,:[264..265] ,) (NNP:[266..271] Tokyo) (NNP:[272..279] Medical) (CC:[280..283] and) (NNP:[284..290] Dental) (NNP:[291..301] University) (NNP:[302..308] School) (IN:[310..312] of) (NNP:[313..321] Medicine) (,:[321..322] ,) (CD:[323..324] 1) (HYPH:[324..325] -) (CD:[325..326] 5) (HYPH:[326..327] -) (CD:[327..329] 45) (NNP:[330..337] Yushima) (,:[337..338] ,) (NNP:[339..345] Bunkyo) (HYPH:[345..346] -) (JJ:[346..348] ku) (,:[348..349] ,) (CD:[350..353] 113) (HYPH:[353..354] -) (CD:[354..358] 8519) (,:[358..359] ,) (NNP:[360..365] Tokyo) (,:[365..366] ,) (NNP:[367..372] Japan) (.:[372..373] .))) ;sentence 4 Span:377..623 ;To clarify the roles of the adenomatous polyposis coli (APC) and beta-catenin ; genes in hereditary nonpolyposis colorectal cancer (HNPCC) tumorigenesis, we ; searched for their mutations in 14 HNPCC adenomas with microsatellite ;instability (MSI). ;[405..431]:gene-rna:"adenomatous polyposis coli" ;[433..436]:gene-rna:"APC" ;[442..454]:gene-rna:"beta-catenin" ;[465..506]:malignancy:"hereditary nonpolyposis colorectal cancer" ;[508..513]:malignancy:"HNPCC" ;[569..616]:malignancy:"HNPCC adenomas with microsatellite instability" (SENT (S (S-PRP (NP-SBJ (-NONE-:[377..377] *)) (VP (TO:[377..379] To) (VP (VB:[380..387] clarify) (NP (NP (DT:[388..391] the) (NNS:[392..397] roles)) (PP (IN:[398..400] of) (PP (DT:[401..404] the) (NML (NML (NML (NML (JJ:[405..416] adenomatous) (NN:[417..426] polyposis) (NN:[427..431] coli)) (NML (-LRB-:[432..433] -LRB-) (NN:[433..436] APC) (-RRB-:[436..437] -RRB-))) (NML-1 (-NONE-:[437..437] *P*))) (CC:[438..441] and) (NML (NN:[442..454] beta-catenin) (NML-1 (NNS:[456..461] genes))))))) (PP (IN:[462..464] in) (NP (NML (NML (JJ:[465..475] hereditary) (JJ:[476..488] nonpolyposis) (JJ:[489..499] colorectal) (NN:[500..506] cancer)) (NML (-LRB-:[507..508] -LRB-) (NN:[508..513] HNPCC) (-RRB-:[513..514] -RRB-))) (NN:[515..528] tumorigenesis)))))) (,:[528..529] ,) (NP-SBJ (PRP:[530..532] we)) (VP (VBD:[534..542] searched) (PP (IN:[543..546] for) (NP (PRP$:[547..552] their) (NNS:[553..562] mutations))) (PP (IN:[563..565] in) (NP (NP (CD:[566..568] 14) (NN:[569..574] HNPCC) (NNS:[575..583] adenomas)) (PP (IN:[584..588] with) (NP (NP (NN:[589..603] microsatellite) (NN:[605..616] instability)) (NP (-LRB-:[617..618] -LRB-) (NN:[618..621] MSI) (-RRB-:[621..622] -RRB-))))))) (.:[622..623] .))) ;sentence 5 Span:624..751 ;Seven (50%) adenomas exhibited somatic APC mutations, five of which were ;frameshift mutations and the other two nonsense ones. ;[636..644]:malignancy:"adenomas" ;[663..666]:gene-rna:"APC" ;[698..718]:variation-type:"frameshift mutations" ;[737..745]:variation-type:"nonsense" (SENT (S (NP-SBJ (CD:[624..629] Seven) (PRN (-LRB-:[630..631] -LRB-) (NP (CD:[631..633] 50) (NN:[633..634] %)) (-RRB-:[634..635] -RRB-)) (NNS:[636..644] adenomas)) (VP (VBD:[645..654] exhibited) (NP (NP (JJ:[655..662] somatic) (NN:[663..666] APC) (NNS:[667..676] mutations)) (,:[676..677] ,) (SBAR (SBAR (WHNP-1 (NP (CD:[678..682] five)) (WHPP (IN:[683..685] of) (WHNP (WDT:[687..692] which)))) (S (NP-SBJ-1 (-NONE-:[692..692] *T*)) (VP (VBD:[693..697] were) (NP-PRD=3 (NN:[698..708] frameshift) (NNS:[709..718] mutations))))) (CC:[719..722] and) (SBAR (WHNP (NP-SBJ=2 (DT:[723..726] the) (JJ:[727..732] other) (CD:[733..736] two))) (S (NP-PRD=3 (JJ:[737..745] nonsense) (NNS:[746..750] ones))))))) (.:[750..751] .))) ;sentence 6 Span:752..859 ;However, the APC mutational spectrum of these adenomas was similar to that ;of sporadic colorectal tumors. ;[766..769]:gene-rna:"APC" ;[799..807]:malignancy:"adenomas" ;[831..858]:malignancy:"sporadic colorectal tumors" (SENT (S (ADVP (RB:[752..759] However)) (,:[759..760] ,) (NP-SBJ (NP (DT:[761..764] the) (NN:[766..769] APC) (JJ:[770..780] mutational) (NN:[781..789] spectrum)) (PP (IN:[790..792] of) (NP (DT:[793..798] these) (NNS:[799..807] adenomas)))) (VP (VBD:[808..811] was) (ADJP-PRD (JJ:[812..819] similar) (PP (TO:[820..822] to) (NP (NP (DT:[823..827] that)) (PP (IN:[828..830] of) (NP (JJ:[831..839] sporadic) (JJ:[841..851] colorectal) (NNS:[852..858] tumors))))))) (.:[858..859] .))) ;sentence 7 Span:860..993 ;Two adenomas (14.3%) with undetectable APC alterations showed missense ;mutations at codon 45 (TCT to TTT or to CCT) in beta-catenin. ;[864..872]:malignancy:"adenomas" ;[899..902]:gene-rna:"APC" ;[923..941]:variation-type:"missense mutations" ;[945..953]:variation-location:"codon 45" ;[955..958]:variation-state-original:"TCT" ;[962..965]:variation-state-altered:"TTT" ;[972..975]:variation-state-altered:"CCT" ;[980..992]:gene-rna:"beta-catenin" (SENT (S (NP-SBJ (NP (CD:[860..863] Two) (NNS:[864..872] adenomas)) (PRN (-LRB-:[873..874] -LRB-) (NP (CD:[874..878] 14.3) (NN:[878..879] %)) (-RRB-:[879..880] -RRB-)) (PP (IN:[881..885] with) (NP (JJ:[886..898] undetectable) (NN:[899..902] APC) (NNS:[903..914] alterations)))) (VP (VBD:[915..921] showed) (NP (JJ:[923..931] missense) (NNS:[932..941] mutations)) (PP-LOC (IN:[942..944] at) (NP (NN:[945..950] codon) (CD:[951..953] 45) (PRN (-LRB-:[954..955] -LRB-) (NP (NP (NN:[955..958] TCT)) (PP (PP (TO:[959..961] to) (NP (NN:[962..965] TTT))) (CC:[966..968] or) (PP (TO:[969..971] to) (NP (NN:[972..975] CCT))))) (-RRB-:[975..976] -RRB-)))) (PP (IN:[977..979] in) (NP (NN:[980..992] beta-catenin)))) (.:[992..993] .))) ;sentence 8 Span:994..1205 ;The MSI frequency in adenomas with beta-catenin mutations was significantly ;higher than that with APCones (P<0.001), indicating that mutations of ;beta-catenin rather than APC are strongly associated with MSI. ;[1016..1024]:malignancy:"adenomas" ;[1030..1042]:gene-rna:"beta-catenin" ;[1094..1097]:gene-rna:"APC" ;[1142..1154]:gene-rna:"beta-catenin" ;[1168..1171]:gene-rna:"APC" (SENT (S (NP-SBJ (NP (DT:[994..997] The) (NN:[998..1001] MSI) (NN:[1003..1012] frequency)) (PP-LOC (IN:[1013..1015] in) (NP (NP (NNS:[1016..1024] adenomas)) (PP (IN:[1025..1029] with) (NP (NN:[1030..1042] beta-catenin) (NNS:[1043..1052] mutations)))))) (VP (VBD:[1053..1056] was) (ADJP-PRD (ADJP (RB:[1057..1070] significantly) (JJR:[1071..1077] higher)) (PP (IN:[1078..1082] than) (NP (NP (DT:[1084..1088] that)) (PP (IN:[1089..1093] with) (NP (NN:[1094..1097] APC) (NNS:[1097..1101] ones)))))) (PRN (-LRB-:[1102..1103] -LRB-) (S (NP-SBJ (NN:[1103..1104] P)) (VP (SYM:[1104..1105] <) (NP (CD:[1105..1110] 0.001)))) (-RRB-:[1110..1111] -RRB-)) (,:[1111..1112] ,) (S-ADV (NP-SBJ (-NONE-:[1112..1112] *)) (VP (VBG:[1113..1123] indicating) (SBAR (IN:[1124..1128] that) (S (NP-SBJ (NP (NNS:[1129..1138] mutations)) (PP (IN:[1139..1141] of) (NP (NP (NN:[1142..1154] beta-catenin)) (PP (IN:[1155..1161] rather) (PP (IN:[1163..1167] than) (NP (NN:[1168..1171] APC))))))) (VP (VBP:[1172..1175] are) (ADVP (RB:[1176..1184] strongly)) (VP (VBN:[1185..1195] associated) (PP-CLR (IN:[1196..1200] with) (NP (NN:[1201..1204] MSI)))))))))) (.:[1204..1205] .))) ;sentence 9 Span:1206..1367 ;These data suggest that adenomas with beta-catenin activating mutations and ;some with APC inactivating mutations may be precursors of HNPCC colorectal ;cancers. ;[1230..1238]:malignancy:"adenomas" ;[1245..1257]:gene-rna:"beta-catenin" ;[1293..1296]:gene-rna:"APC" ;[1342..1366]:malignancy:"HNPCC colorectal cancers" (SENT (S (NP-SBJ (DT:[1206..1211] These) (NNS:[1212..1216] data)) (VP (VBP:[1217..1224] suggest) (SBAR (IN:[1225..1229] that) (S (NP-SBJ (NP (NP (NNS:[1230..1238] adenomas)) (PP (IN:[1239..1243] with) (NP (NN:[1245..1257] beta-catenin) (VBG:[1258..1268] activating) (NNS:[1269..1278] mutations)))) (CC:[1279..1282] and) (NP (NP (DT:[1283..1287] some)) (PP (IN:[1288..1292] with) (NP (NN:[1293..1296] APC) (VBG:[1297..1309] inactivating) (NNS:[1310..1319] mutations))))) (VP (MD:[1320..1323] may) (VP (VB:[1325..1327] be) (NP-PRD (NP (NNS:[1328..1338] precursors)) (PP (IN:[1339..1341] of) (NP (NN:[1342..1347] HNPCC) (JJ:[1348..1358] colorectal) (NNS:[1359..1366] cancers))))))))) (.:[1366..1367] .))) ;section 10 Span:1371..1416 ;PMID: 10936679 [PubMed - indexed for MEDLINE] (SEC (FRAG (NNP:[1371..1375] PMID) (::[1375..1376] :) (CD:[1377..1385] 10936679) (IN:[1386..1387] -LSB-) (NNP:[1387..1393] PubMed) (HYPH:[1394..1395] -) (JJ:[1396..1403] indexed) (IN:[1404..1407] for) (NNP:[1408..1416] MEDLINE-RSB-)))