;PMID: 8843915 ;source_file_1309.mrg ;Release 0.9 of PennBioIE ;Funded by NSF ITR EIA-0205448 ;0)section:[e:0..49] = [t:0..49] ;1)sentence:[e:54..125] = [t:54..125] ;2)section:[e:129..184] = [t:129..184] ;3)section:[e:188..289] = [t:188..289] ;4)sentence:[e:293..301] = [t:293..301] ;5)sentence:[e:302..468] = [t:302..468] ;6)sentence:[e:469..477] = [t:469..477] ;7)sentence:[e:478..562] = [t:478..562] ;8)sentence:[e:563..729] = [t:563..729] ;9)sentence:[e:730..856] = [t:730..856] ;10)sentence:[e:857..865] = [t:857..865] ;11)sentence:[e:866..966] = [t:866..966] ;12)sentence:[e:967..1064] = [t:967..1064] ;13)sentence:[e:1065..1209] = [t:1065..1209] ;14)sentence:[e:1211..1301] = [t:1211..1301] ;15)sentence:[e:1302..1314] = [t:1302..1314] ;16)sentence:[e:1315..1436] = [t:1315..1436] ;17)sentence:[e:1437..1537] = [t:1437..1537] ;18)sentence:[e:1538..1650] = [t:1538..1650] ;19)sentence:[e:1651..1758] = [t:1651..1758] ;20)section:[e:1762..1806] = [t:1762..1806] ;section 0 Span:0..49 ;Invest Ophthalmol Vis Sci 1996 Oct;37(11):2313-7 (SEC (FRAG (NNP:[0..6] Invest) (NNP:[7..17] Ophthalmol) (NNP:[18..21] Vis) (NNP:[22..25] Sci) (CD:[27..31] 1996) (.:[32..38] Oct;37) (-LRB-:[38..39] -LRB-) (CD:[39..41] 11) (-RRB-:[41..42] -RRB-) (::[42..43] :) (CD:[43..49] 2313-7))) ;sentence 1 Span:54..125 ;Identification of mutations in the Ki-ras gene in human retinoblastoma. ;[89..95]:gene-rna:"Ki-ras" ;[110..124]:malignancy-type:"retinoblastoma" (SENT (NP-HLN (NP (NN:[54..68] Identification)) (PP (IN:[69..71] of) (NP (NP (NNS:[72..81] mutations)) (PP-LOC (IN:[82..84] in) (NP (DT:[85..88] the) (NN:[89..95] Ki-ras) (NN:[96..100] gene))))) (PP (IN:[101..103] in) (NP (JJ:[104..109] human) (NN:[110..124] retinoblastoma))) (.:[124..125] .))) ;section 2 Span:129..184 ;Bautista D, Emanuel JR, Granville C, Howard R, Costa J. (SEC (FRAG (NNP:[129..137] Bautista) (NNP:[138..139] D) (,:[139..140] ,) (NNP:[141..148] Emanuel) (NNP:[149..151] JR) (,:[151..152] ,) (NNP:[153..162] Granville) (NNP:[163..164] C) (,:[164..165] ,) (NNP:[166..172] Howard) (NNP:[173..174] R) (,:[174..175] ,) (NNP:[176..181] Costa) (NNP:[182..184] J.))) ;section 3 Span:188..289 ;Department of Pathology, Yale University School of Medicine, New Haven, ;Connecticut 06520-8023, USA. (SEC (FRAG (NNP:[188..198] Department) (IN:[199..201] of) (NNP:[202..211] Pathology) (,:[211..212] ,) (NNP:[213..217] Yale) (NNP:[218..228] University) (NNP:[229..235] School) (IN:[236..238] of) (NNP:[239..247] Medicine) (,:[247..248] ,) (NNP:[249..252] New) (NNP:[253..258] Haven) (,:[258..259] ,) (NNP:[261..272] Connecticut) (CD:[273..278] 06520) (HYPH:[278..279] -) (CD:[279..283] 8023) (,:[283..284] ,) (NNP:[285..288] USA) (.:[288..289] .))) ;sentence 4 Span:293..301 ;PURPOSE: (SENT (NP (NN:[293..300] PURPOSE) (::[300..301] :))) ;sentence 5 Span:302..468 ;To investigate the mutational status of the Ki-ras gene in retinoblastoma ;and to evaluate a correlation of the genotype with clinical and ;histopathologic variables. ;[346..352]:gene-rna:"Ki-ras" ;[362..376]:malignancy-type:"retinoblastoma" (SENT (S (NP-SBJ (-NONE-:[302..302] *)) (VP (VP (TO:[302..304] To) (VP (VB:[305..316] investigate) (NP (NP (DT:[317..320] the) (JJ:[321..331] mutational) (NN:[332..338] status)) (PP (IN:[339..341] of) (NP (DT:[342..345] the) (NN:[346..352] Ki-ras) (NN:[353..357] gene)))) (PP (IN:[358..360] in) (NP (NN:[362..376] retinoblastoma))))) (CC:[377..380] and) (VP (TO:[381..383] to) (VP (VB:[384..392] evaluate) (NP (NP (DT:[393..394] a) (NN:[395..406] correlation)) (PP (IN:[407..409] of) (NP (DT:[410..413] the) (NN:[414..422] genotype))) (PP (IN:[423..427] with) (NP (ADJP (JJ:[428..436] clinical) (CC:[437..440] and) (JJ:[442..457] histopathologic)) (NNS:[458..467] variables))))))) (.:[467..468] .))) ;sentence 6 Span:469..477 ;METHODS: (SENT (NP (NNS:[469..476] METHODS) (::[476..477] :))) ;sentence 7 Span:478..562 ;Tumor samples were microdissected from sectioned archival paraffin-embedded ;tissue. (SENT (S (NP-SBJ-1 (NN:[478..483] Tumor) (NNS:[484..491] samples)) (VP (VBD:[492..496] were) (VP (VBN:[497..511] microdissected) (NP-1 (-NONE-:[511..511] *)) (PP (IN:[512..516] from) (NP (VBN:[518..527] sectioned) (JJ:[528..536] archival) (ADJP (NN:[537..545] paraffin) (HYPH:[545..546] -) (VBN:[546..554] embedded)) (NN:[555..561] tissue))))) (.:[561..562] .))) ;sentence 8 Span:563..729 ;Ki-ras genomic sequences (exons 1 and 2) were amplified by polymerase chain ;reaction then analyzed by single-strand conformation polymorphism and direct ;sequencing. ;[563..569]:gene-rna:"Ki-ras" ;[589..596]:variation-location:"exons 1" ;[589..594]...[602..603]:variation-location:"exons"..."2" ;[623..633]:gene-protein:"polymerase" (SENT (S (NP-SBJ-2 (NN:[563..569] Ki-ras) (JJ:[570..577] genomic) (NNS:[578..587] sequences) (PRN (-LRB-:[588..589] -LRB-) (NP (NP (NML-1 (NNS:[589..594] exons)) (CD:[595..596] 1)) (CC:[598..601] and) (NP (NML-1 (-NONE-:[601..601] *P*)) (CD:[602..603] 2))) (-RRB-:[603..604] -RRB-))) (VP (VBD:[605..609] were) (VP (VP (VBN:[610..619] amplified) (NP-2 (-NONE-:[619..619] *)) (PP-MNR (IN:[620..622] by) (NP (NN:[623..633] polymerase) (NN:[634..639] chain) (NN:[640..648] reaction)))) (VP (ADVP-TMP (RB:[649..653] then)) (VBN:[654..662] analyzed) (NP-2 (-NONE-:[662..662] *)) (PP-MNR (IN:[663..665] by) (NP (NP (NML (JJ:[667..673] single) (HYPH:[673..674] -) (NN:[674..680] strand)) (NN:[681..693] conformation) (NN:[694..706] polymorphism)) (CC:[707..710] and) (NP (JJ:[711..717] direct) (NN:[718..728] sequencing))))))) (.:[728..729] .))) ;sentence 9 Span:730..856 ;Tissue sections, flanking the analyzed samples, were stained with ;hematoxylin and eosin for examination by light microscopy. (SENT (S (NP-SBJ-1 (NP (NN:[730..736] Tissue) (NNS:[737..745] sections)) (,:[745..746] ,) (VP (VBG:[748..756] flanking) (NP (DT:[757..760] the) (VBN:[761..769] analyzed) (NNS:[770..777] samples)))) (,:[777..778] ,) (VP (VBD:[779..783] were) (VP (VBN:[784..791] stained) (NP-1 (-NONE-:[791..791] *)) (PP (IN:[792..796] with) (NP (NN:[797..808] hematoxylin) (CC:[809..812] and) (NN:[813..818] eosin))) (PP (IN:[819..822] for) (NP (NP (NN:[824..835] examination)) (PP (IN:[836..838] by) (NP (NN:[839..844] light) (NN:[845..855] microscopy))))))) (.:[855..856] .))) ;sentence 10 Span:857..865 ;RESULTS: (SENT (NP (NNS:[857..864] RESULTS) (::[864..865] :))) ;sentence 11 Span:866..966 ;Four of 12 tumors had mutation in exon 1, codon 12 of the Ki-ras gene; none ;had mutation in exon 2. ;[888..896]:variation-event:"mutation" ;[900..907]:variation-location:"exon 1" ;[909..917]:variation-location:"codon 12" ;[925..931]:gene-rna:"Ki-ras" ;[947..955]:variation-event:"mutation" ;[959..965]:variation-location:"exon 2" (SENT (S (S (NP-SBJ (NP (CD:[866..870] Four)) (PP (IN:[871..873] of) (NP (CD:[874..876] 12) (NNS:[877..883] tumors)))) (VP (VBD:[884..887] had) (NP (NN:[888..896] mutation)) (PP-LOC (IN:[897..899] in) (NP (NP (NN:[900..904] exon) (CD:[906..907] 1)) (,:[907..908] ,) (NP (NN:[909..914] codon) (CD:[915..917] 12)) (PP (IN:[918..920] of) (NP (DT:[921..924] the) (NN:[925..931] Ki-ras) (NN:[932..936] gene))))))) (::[936..937] ;) (S (NP-SBJ (NN:[938..942] none)) (VP (VBD:[943..946] had) (NP (NN:[947..955] mutation)) (PP-LOC (IN:[956..958] in) (NP (NN:[959..963] exon) (CD:[964..965] 2))))) (.:[965..966] .))) ;sentence 12 Span:967..1064 ;Signal intensity of the mutated alleles indicates clonal mutation in the ;tumor cell populations. (SENT (S (NP-SBJ (NP (NN:[967..973] Signal) (NN:[974..983] intensity)) (PP (IN:[984..986] of) (NP (DT:[988..991] the) (VBN:[992..999] mutated) (NNS:[1000..1007] alleles)))) (VP (VBZ:[1008..1017] indicates) (NP (JJ:[1018..1024] clonal) (NN:[1025..1033] mutation)) (PP (IN:[1034..1036] in) (NP (DT:[1037..1040] the) (NN:[1041..1046] tumor) (NN:[1047..1051] cell) (NNS:[1052..1063] populations)))) (.:[1063..1064] .))) ;sentence 13 Span:1065..1209 ;One of four bilateral tumors was mutated, and all three samples with ;undifferentiated histologic appearance harbored a clonal Ki-ras mutation. ;[1078..1094]:malignancy-type:"bilateral tumors" ;[1193..1199]:gene-rna:"Ki-ras" (SENT (S (S (NP-SBJ-1 (NP (CD:[1065..1068] One)) (PP (IN:[1070..1072] of) (NP (CD:[1073..1077] four) (JJ:[1078..1087] bilateral) (NNS:[1088..1094] tumors)))) (VP (VBD:[1095..1098] was) (VP (VBN:[1099..1106] mutated) (NP-1 (-NONE-:[1106..1106] *))))) (,:[1106..1107] ,) (CC:[1108..1111] and) (S (NP-SBJ (NP (DT:[1112..1115] all) (CD:[1116..1121] three) (NNS:[1122..1129] samples)) (PP (IN:[1130..1134] with) (NP (JJ:[1136..1152] undifferentiated) (JJ:[1153..1163] histologic) (NN:[1164..1174] appearance)))) (VP (VBD:[1175..1183] harbored) (NP (DT:[1184..1185] a) (JJ:[1186..1192] clonal) (NN:[1193..1199] Ki-ras) (NN:[1200..1208] mutation)))) (.:[1208..1209] .))) ;sentence 14 Span:1211..1301 ;However, only one of nine moderately to poorly differentiated tumors harbored ;a mutation. (SENT (S (ADVP (RB:[1211..1218] However)) (,:[1218..1219] ,) (NP-SBJ (NP (RB:[1220..1224] only) (CD:[1225..1228] one)) (PP (IN:[1229..1231] of) (NP (CD:[1232..1236] nine) (ADJP (ADVP (RB:[1237..1247] moderately) (TO:[1248..1250] to) (RB:[1251..1257] poorly)) (VBN:[1258..1272] differentiated)) (NNS:[1273..1279] tumors)))) (VP (VBD:[1280..1288] harbored) (NP (DT:[1289..1290] a) (NN:[1292..1300] mutation))) (.:[1300..1301] .))) ;sentence 15 Span:1302..1314 ;CONCLUSIONS: (SENT (NP (NNS:[1302..1313] CONCLUSIONS) (::[1313..1314] :))) ;sentence 16 Span:1315..1436 ;Ki-ras, an oncogene seldom altered in neuroectodermal neoplasms, is mutated ;in one third of the retinoblastomas studied. ;[1315..1321]:gene-rna:"Ki-ras" ;[1353..1379]:malignancy-type:"neuroectodermal neoplasms" ;[1412..1427]:malignancy-type:"retinoblastomas" (SENT (S (NP-SBJ-1 (NP (NN:[1315..1321] Ki-ras)) (,:[1321..1322] ,) (NP (NP (DT:[1323..1325] an) (NN:[1326..1334] oncogene)) (VP (ADVP-TMP (RB:[1335..1341] seldom)) (VBN:[1342..1349] altered) (NP (-NONE-:[1349..1349] *)) (PP-LOC (IN:[1350..1352] in) (NP (JJ:[1353..1368] neuroectodermal) (NNS:[1370..1379] neoplasms)))))) (,:[1379..1380] ,) (VP (VBZ:[1381..1383] is) (VP (VBN:[1384..1391] mutated) (NP-1 (-NONE-:[1391..1391] *)) (PP (IN:[1392..1394] in) (NP (NP (CD:[1395..1398] one) (NN:[1399..1404] third)) (PP (IN:[1405..1407] of) (NP (NP (DT:[1408..1411] the) (NNS:[1412..1427] retinoblastomas)) (VP (VBN:[1428..1435] studied) (NP (-NONE-:[1435..1435] *))))))))) (.:[1435..1436] .))) ;sentence 17 Span:1437..1537 ;The Ki-ras mutations are clonal, suggesting that affected cells have a ;selective growth advantage. ;[1441..1447]:gene-rna:"Ki-ras" ;[1449..1458]:variation-event:"mutations" (SENT (S (NP-SBJ (DT:[1437..1440] The) (NN:[1441..1447] Ki-ras) (NNS:[1449..1458] mutations)) (VP (VBP:[1459..1462] are) (ADJP-PRD (JJ:[1463..1469] clonal)) (,:[1469..1470] ,) (S-ADV (NP-SBJ (-NONE-:[1470..1470] *)) (VP (VBG:[1471..1481] suggesting) (SBAR (IN:[1482..1486] that) (S (NP-SBJ (VBN:[1487..1495] affected) (NNS:[1496..1501] cells)) (VP (VBP:[1502..1506] have) (NP (DT:[1507..1508] a) (JJ:[1509..1518] selective) (NN:[1519..1525] growth) (NN:[1527..1536] advantage)))))))) (.:[1536..1537] .))) ;sentence 18 Span:1538..1650 ;The mutations are present and are likely to play a pathogenetic role in ;heritable and sporadic retinoblastomas. ;[1542..1551]:variation-event:"mutations" ;[1634..1649]:malignancy-type:"retinoblastomas" (SENT (S (NP-SBJ-1 (DT:[1538..1541] The) (NNS:[1542..1551] mutations)) (VP (VP (VBP:[1552..1555] are) (ADJP-PRD (JJ:[1556..1563] present))) (CC:[1564..1567] and) (VP (VBP:[1568..1571] are) (ADJP-PRD (JJ:[1572..1578] likely) (S (NP-SBJ-1 (-NONE-:[1578..1578] *)) (VP (TO:[1579..1581] to) (VP (VB:[1582..1586] play) (NP (DT:[1587..1588] a) (JJ:[1589..1601] pathogenetic) (NN:[1602..1606] role)) (PP (IN:[1608..1610] in) (NP (NP (JJ:[1611..1620] heritable) (NML-2 (-NONE-:[1620..1620] *P*))) (CC:[1621..1624] and) (NP (JJ:[1625..1633] sporadic) (NML-2 (NNS:[1634..1649] retinoblastomas))))))))))) (.:[1649..1650] .))) ;sentence 19 Span:1651..1758 ;These results suggest that mutations in Ki-ras are preferentially associated ;with undifferentiated tumors. ;[1692..1698]:gene-rna:"Ki-ras" (SENT (S (NP-SBJ (DT:[1651..1656] These) (NNS:[1657..1664] results)) (VP (VBP:[1665..1672] suggest) (SBAR (IN:[1673..1677] that) (S (NP-SBJ-1 (NP (NNS:[1678..1687] mutations)) (PP-LOC (IN:[1689..1691] in) (NP (NN:[1692..1698] Ki-ras)))) (VP (VBP:[1699..1702] are) (ADVP (RB:[1703..1717] preferentially)) (VP (VBN:[1718..1728] associated) (NP-1 (-NONE-:[1728..1728] *)) (PP-CLR (IN:[1729..1733] with) (NP (JJ:[1734..1750] undifferentiated) (NNS:[1751..1757] tumors)))))))) (.:[1757..1758] .))) ;section 20 Span:1762..1806 ;PMID: 8843915 [PubMed - indexed for MEDLINE] (SEC (FRAG (NNP:[1762..1766] PMID) (::[1766..1767] :) (CD:[1768..1775] 8843915) (NN:[1776..1777] -LSB-) (NNP:[1777..1783] PubMed) (::[1784..1785] -) (NN:[1786..1793] indexed) (IN:[1794..1797] for) (NNP:[1798..1806] MEDLINE-RSB-)))