;PMID: 11048799
;source_file_1208.mrg
;Release 0.9 of PennBioIE
;Funded by NSF ITR EIA-0205448

;0)section:[e:0..35] = [t:0..35]
;1)sentence:[e:40..123] = [t:40..123]
;2)section:[e:127..177] = [t:127..177]
;3)section:[e:181..286] = [t:181..286]
;4)sentence:[e:290..451] = [t:290..451]
;5)sentence:[e:452..754] = [t:452..754]
;6)sentence:[e:755..982] = [t:755..982]
;7)sentence:[e:983..1211] = [t:983..1211]
;8)sentence:[e:1213..1297] = [t:1213..1297]
;9)sentence:[e:1298..1422] = [t:1298..1422]
;10)sentence:[e:1423..1559] = [t:1423..1559]
;11)sentence:[e:1560..1663] = [t:1560..1663]
;12)sentence:[e:1664..1732] = [t:1664..1732]
;13)sentence:[e:1733..1868] = [t:1733..1868]
;14)section:[e:1872..1917] = [t:1872..1917]

;section 0 Span:0..35
;Mod Pathol  2000 Oct;13(10):1066-71
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        (CD:[27..32] :1066) (HYPH:[32..33] -) (CD:[33..35] 71)))

;sentence 1 Span:40..123
;Mutational analysis of the CTNNB1 and APC genes in uterine endometrioid 
;carcinoma.
;[67..73]:gene-rna:"CTNNB1"
;[78..81]:gene-rna:"APC"
;[91..122]:malignancy:"uterine endometrioid  carcinoma"
(SENT
  (NP-HLN
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          (NML (NN:[67..73] CTNNB1)
            (NML-1 (-NONE-:[73..73] *P*)))
          (CC:[74..77] and)
          (NML (NN:[78..81] APC)
            (NML-1 (NNS:[82..87] genes))))))
    (PP (IN:[88..90] in)
      (NP (JJ:[91..98] uterine) (JJ:[99..111] endometrioid)
          (NN:[113..122] carcinoma)))
    (.:[122..123] .)))

;section 2 Span:127..177
;Schlosshauer PW, Pirog EC, Levine RL, Ellenson LH.
(SEC
  (FRAG (NNP:[127..139] Schlosshauer) (NNP:[140..142] PW) (,:[142..143] ,)
        (NNP:[144..149] Pirog) (NNP:[150..152] EC) (,:[152..153] ,)
        (NNP:[154..160] Levine) (NNP:[161..163] RL) (,:[163..164] ,)
        (NNP:[165..173] Ellenson) (NNP:[174..177] LH.)))

;section 3 Span:181..286
;Department of Pathology, Joan and Sanford I. Weill Medical College of Cornell
; University, New York, USA.
(SEC
  (FRAG (NNP:[181..191] Department) (IN:[192..194] of)
        (NNP:[195..204] Pathology) (,:[204..205] ,) (NNP:[206..210] Joan)
        (CC:[211..214] and) (NNP:[215..222] Sanford) (NNP:[223..224] I)
        (.:[224..225] .) (NNP:[226..231] Weill) (NNP:[232..239] Medical)
        (NNP:[240..247] College) (IN:[248..250] of) (NNP:[251..258] Cornell)
        (NNP:[260..270] University) (,:[270..271] ,) (NNP:[272..275] New)
        (NNP:[276..280] York) (,:[280..281] ,) (NNP:[282..285] USA)
        (.:[285..286] .)))

;sentence 4 Span:290..451
;Despite recent studies, the molecular genetic events responsible for the 
;development of uterine endometrioid carcinoma (UEC) remain incompletely 
;characterized.
;[379..409]:malignancy:"uterine endometrioid carcinoma"
;[411..414]:malignancy:"UEC"
(SENT
  (S
    (PP (IN:[290..297] Despite)
      (NP (JJ:[298..304] recent) (NNS:[305..312] studies)))
    (,:[312..313] ,)
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          (NNS:[336..342] events))
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            (PP (IN:[376..378] of)
              (NP
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                    (NN:[400..409] carcinoma))
                (NP (-LRB-:[410..411] -LRB-)
                  (NP (NN:[411..414] UEC))
                  (-RRB-:[414..415] -RRB-))))))))
    (VP (VBP:[416..422] remain)
      (ADJP-PRD (RB:[423..435] incompletely) (VBN:[437..450] characterized)))
    (.:[450..451] .)))

;sentence 5 Span:452..754
;Mutations in the beta-catenin (CTNNB1) gene have been recently  reported in a
;small percentage of UECs and in the endometrioid variant of  ovarian
;carcinoma suggesting that the Wnt signal transduction pathway is  involved in
;the development of female genital tract tumors with endometrioid 
;morphology.
;[469..481]:gene-rna:"beta-catenin"
;[483..489]:gene-rna:"CTNNB1"
;[550..554]:malignancy:"UECs"
;[566..608]:malignancy:"endometrioid variant of  ovarian carcinoma"
;[629..632]:gene-generic:"Wnt"
;[696..723]...[729..741]:malignancy:"female genital tract
;tumors"..."endometrioid"
(SENT
  (S
    (NP-SBJ-1
      (NP (NNS:[452..461] Mutations))
      (PP (IN:[462..464] in)
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            (NML (-LRB-:[482..483] -LRB-) (NN:[483..489] CTNNB1)
                 (-RRB-:[489..490] -RRB-)))
          (NN:[491..495] gene))))
    (VP (VBP:[496..500] have)
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              (NP
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                    (NN:[536..546] percentage))
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            (CC:[555..558] and)
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              (NP
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                    (NN:[579..586] variant))
                (PP (IN:[587..589] of)
                  (NP (JJ:[591..598] ovarian) (NN:[599..608] carcinoma))))))
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            (VP (VBG:[609..619] suggesting)
              (SBAR (IN:[620..624] that)
                (S
                  (NP-SBJ-2 (DT:[625..628] the) (NN:[629..632] Wnt)
                    (NML (NN:[633..639] signal) (NN:[640..652] transduction))
                    (NN:[653..660] pathway))
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                          (PP (IN:[693..695] of)
                            (NP
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                                (NML (JJ:[703..710] genital)
                                     (NN:[711..716] tract))
                                (NNS:[717..723] tumors))
                              (PP (IN:[724..728] with)
                                (NP (JJ:[729..741] endometrioid)
                                    (NN:[743..753] morphology))))))))))))))))
    (.:[753..754] .)))

;sentence 6 Span:755..982
;The Wnt pathway is a critical pathway in the development of  colorectal
;cancer (CRC) with mutations occurring in the beta-catenin (CTNNB1) or 
;adenomatous polyposis coli (APC) genes in 10 to 15% and 85% of cases, 
;respectively.
;[759..762]:gene-generic:"Wnt"
;[816..833]:malignancy:"colorectal cancer"
;[835..838]:malignancy:"CRC"
;[872..884]:gene-rna:"beta-catenin"
;[886..892]:gene-rna:"CTNNB1"
;[898..924]:gene-rna:"adenomatous polyposis coli"
;[926..929]:gene-rna:"APC"
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  (S
    (NP-SBJ (DT:[755..758] The) (NN:[759..762] Wnt) (NN:[763..770] pathway))
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        (NP
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          (VP (VBG:[855..864] occurring)
            (PP (IN:[865..867] in)
              (NP (DT:[868..871] the)
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                      (NML (-LRB-:[885..886] -LRB-) (NN:[886..892] CTNNB1)
                           (-RRB-:[892..893] -RRB-)))
                    (NML-1 (-NONE-:[893..893] *P*)))
                  (CC:[894..896] or)
                  (NML
                    (NML
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                           (NN:[920..924] coli))
                      (NML (-LRB-:[925..926] -LRB-) (NN:[926..929] APC)
                           (-RRB-:[929..930] -RRB-)))
                    (NML-1 (NNS:[931..936] genes)))))))))
      (PP (IN:[937..939] in)
        (NP
          (NP
            (QP (CD:[940..942] 10) (TO:[943..945] to) (CD:[946..948] 15))
            (NN:[948..949] %))
          (CC:[950..953] and)
          (NP
            (NP (CD:[954..956] 85) (NN:[956..957] %))
            (PP (IN:[958..960] of)
              (NP (NNS:[961..966] cases))))))
      (,:[966..967] ,)
      (ADVP (RB:[969..981] respectively)))
    (.:[981..982] .)))

;sentence 7 Span:983..1211
;Because UEC and CRC share other molecular genetic alterations and  histologic
;features and previous studies of UEC have not reported an analysis of  the
;APC gene, we chose to further elucidate the role of the Wnt pathway in UEC.
;[991..994]:malignancy:"UEC"
;[999..1002]:malignancy:"CRC"
;[1094..1097]:malignancy:"UEC"
;[1136..1139]:gene-rna:"APC"
;[1192..1195]:gene-generic:"Wnt"
;[1207..1210]:malignancy:"UEC"
(SENT
  (S
    (SBAR-PRP (IN:[983..990] Because)
      (S
        (S
          (NP-SBJ (NN:[991..994] UEC) (CC:[995..998] and) (NN:[999..1002] CRC))
          (VP (VBP:[1003..1008] share)
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              (NP (JJ:[1009..1014] other) (JJ:[1015..1024] molecular)
                  (JJ:[1025..1032] genetic) (NNS:[1033..1044] alterations))
              (CC:[1045..1048] and)
              (NP (JJ:[1050..1060] histologic) (NNS:[1061..1069] features)))))
        (CC:[1070..1073] and)
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                      (NN:[1140..1144] gene)))))))))
    (,:[1144..1145] ,)
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      (S
        (NP-SBJ (-NONE-:[1154..1154] *))
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                    (NN:[1196..1203] pathway)))
              (PP (IN:[1204..1206] in)
                (NP (NN:[1207..1210] UEC))))))))
    (.:[1210..1211] .)))

;sentence 8 Span:1213..1297
;To this end, we analyzed 32 cases of UEC for mutations of the CTNNB1 and APC 
;genes.
;[1250..1253]:malignancy:"UEC"
;[1275..1281]:gene-rna:"CTNNB1"
;[1286..1289]:gene-rna:"APC"
(SENT
  (S
    (PP (TO:[1213..1215] To)
      (NP (DT:[1216..1220] this) (NN:[1221..1224] end)))
    (,:[1224..1225] ,)
    (NP-SBJ (PRP:[1226..1228] we))
    (VP (VBD:[1229..1237] analyzed)
      (NP
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      (PP (IN:[1254..1257] for)
        (NP
          (NP (NNS:[1258..1267] mutations))
          (PP (IN:[1268..1270] of)
            (NP (DT:[1271..1274] the)
              (NML
                (NML (NN:[1275..1281] CTNNB1)
                  (NML-1 (-NONE-:[1281..1281] *P*)))
                (CC:[1282..1285] and)
                (NML (NN:[1286..1289] APC)
                  (NML-1 (NNS:[1291..1296] genes)))))))))
    (.:[1296..1297] .)))

;sentence 9 Span:1298..1422
;Mutations of CTNNB1 were present in six of 32 (18%) cases: four grade 1 
;carcinomas, one grade 2, and one grade 3 carcinoma.
;[1311..1317]:gene-rna:"CTNNB1"
;[1362..1381]:malignancy:"grade 1  carcinomas"
;[1387..1394]...[1412..1421]:malignancy:"grade 2"..."carcinoma"
;[1404..1421]:malignancy:"grade 3 carcinoma"
(SENT
  (S
    (NP-SBJ
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        (NP (NN:[1311..1317] CTNNB1))))
    (VP (VBD:[1318..1322] were)
      (ADJP-PRD (JJ:[1323..1330] present)
        (PP (IN:[1331..1333] in)
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              (PP (IN:[1338..1340] of)
                (NP (CD:[1341..1343] 32)
                  (PRN (-LRB-:[1344..1345] -LRB-)
                    (NP (CD:[1345..1347] 18) (NN:[1347..1348] %))
                    (-RRB-:[1348..1349] -RRB-))
                  (NNS:[1350..1355] cases))))
            (::[1355..1356] :)
            (NP (CD:[1357..1361] four)
              
              (NML (NN:[1362..1367] grade) (CD:[1368..1369] 1))
              (NML (NNS:[1371..1381] carcinomas)))
            (,:[1381..1382] ,)
            (NP (CD:[1383..1386] one)
              (NML (NN:[1387..1392] grade) (CD:[1393..1394] 2)))
            (,:[1394..1395] ,) (CC:[1396..1399] and)
            (NP (CD:[1400..1403] one)
              
              (NML (NN:[1404..1409] grade) (CD:[1410..1411] 3))
              (NN:[1412..1421] carcinoma))))))
    (.:[1421..1422] .)))

;sentence 10 Span:1423..1559
;Five missense mutations were  identified, three involving Ser/Thr
;phosphorylation sites and two adjacent to a  Ser phosphorylation site.
;[1428..1446]:variation-type:"missense mutations"
(SENT
  (S
    (NP-SBJ-1
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                   (NN:[1485..1488] Thr))
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                  (NN:[1538..1553] phosphorylation) (NN:[1554..1558] site)))))))
    (.:[1558..1559] .)))

;sentence 11 Span:1560..1663
;One case contained a deletion encompassing codons 34  to 37, which includes a
;Ser phosphorylation site.
;[1581..1589]:variation-type:"deletion"
;[1603..1619]:variation-location:"codons 34  to 37"
(SENT
  (S
    (NP-SBJ (CD:[1560..1563] One) (NN:[1564..1568] case))
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            (NP
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                  (NN:[1642..1657] phosphorylation) (NN:[1658..1662] site)))))))
    (.:[1662..1663] .)))

;sentence 12 Span:1664..1732
;No mutations resulting in  truncation of the APC protein were found.
;[1667..1676]:variation-event:"mutations"
;[1709..1712]:gene-protein:"APC"
(SENT
  (S
    (NP-SBJ-1
      (NP (DT:[1664..1666] No) (NNS:[1667..1676] mutations))
      (VP (VBG:[1677..1686] resulting)
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            (PP (IN:[1702..1704] of)
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        (NP-1 (-NONE-:[1731..1731] *))))
    (.:[1731..1732] .)))

;sentence 13 Span:1733..1868
;Our results support a role for the Wnt  signaling pathway via mutation of
;CTNNB1, but not APC, in the development of a  subset of UECs.
;[1768..1771]:gene-generic:"Wnt"
;[1807..1813]:gene-rna:"CTNNB1"
;[1823..1826]:gene-rna:"APC"
;[1863..1867]:malignancy:"UECs"
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        (PP (IN:[1760..1763] for)
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            (PP (IN:[1804..1806] of)
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                (CONJP (CC:[1815..1818] but) (RB:[1819..1822] not))
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        (,:[1826..1827] ,)
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                (PP (IN:[1860..1862] of)
                  (NP (NNS:[1863..1867] UECs)))))))))
    (.:[1867..1868] .)))

;section 14 Span:1872..1917
;PMID: 11048799 [PubMed - indexed for MEDLINE]
(SEC
  (FRAG (NNP:[1872..1876] PMID) (::[1876..1877] :) (CD:[1878..1886] 11048799)
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