;PMID: 8161790 ;source_file_1231.mrg ;Release 0.9 of PennBioIE ;Funded by NSF ITR EIA-0205448 ;0)section:[e:0..32] = [t:0..32] ;1)sentence:[e:37..106] = [t:37..106] ;2)section:[e:110..176] = [t:110..176] ;3)section:[e:180..263] = [t:180..263] ;4)sentence:[e:267..487] = [t:267..487] ;5)sentence:[e:488..667] = [t:488..667] ;6)sentence:[e:669..894] = [t:669..894] ;7)sentence:[e:896..1024] = [t:896..1024] ;8)sentence:[e:1025..1174] = [t:1025..1174] ;9)sentence:[e:1175..1335] = [t:1175..1335] ;10)sentence:[e:1336..1514] = [t:1336..1514] ;11)section:[e:1518..1562] = [t:1518..1562] ;section 0 Span:0..32 ;Blood 1994 Apr 15;83(8):2248-54 (SEC (FRAG (NNP:[0..5] Blood) (CD:[7..11] 1994) (NNP:[12..15] Apr) (CD:[16..18] 15) (CC:[18..22] ;83-LRB-) (CD:[22..23] 8) (-RRB-:[23..24] -RRB-) (CD:[24..29] :2248) (::[29..30] -) (CD:[30..32] 54))) ;sentence 1 Span:37..106 ;Mutations of the N-ras gene in juvenile chronic myelogenous leukemia. ;[54..59]:gene-rna:"N-ras" ;[68..105]:malignancy:"juvenile chronic myelogenous leukemia" (SENT (NP-HLN (NP (NNS:[37..46] Mutations)) (PP (IN:[47..49] of) (NP (DT:[50..53] the) (NN:[54..59] N-ras) (NN:[60..64] gene))) (PP (IN:[65..67] in) (NP (JJ:[68..76] juvenile) (JJ:[77..84] chronic) (JJ:[85..96] myelogenous) (NN:[97..105] leukemia))) (.:[105..106] .))) ;section 2 Span:110..176 ;Miyauchi J, Asada M, Sasaki M, Tsunematsu Y, Kojima S, Mizutani S. (SEC (FRAG (NNP:[110..118] Miyauchi) (NNP:[119..121] J,) (NNP:[122..127] Asada) (NNP:[128..130] M,) (NNP:[131..137] Sasaki) (NNP:[138..140] M,) (NNP:[141..151] Tsunematsu) (NNP:[152..153] Y) (,:[153..154] ,) (NNP:[155..161] Kojima) (NNP:[162..164] S,) (NNP:[165..173] Mizutani) (NNP:[174..176] S.))) ;section 3 Span:180..263 ;Department of Virology, National Children's Medical Research Center, Tokyo, ;Japan. (SEC (FRAG (NNP:[180..190] Department) (IN:[191..193] of) (NNP:[194..202] Virology) (,:[202..203] ,) (NNP:[204..212] National) (NNP:[213..221] Children) (POS:[221..223] 's) (NNP:[224..231] Medical) (NNP:[232..240] Research) (NNP:[241..247] Center) (,:[247..248] ,) (NNP:[249..254] Tokyo) (,:[254..255] ,) (NNP:[257..262] Japan) (.:[262..263] .))) ;sentence 4 Span:267..487 ;Juvenile chronic myelogenous leukemia (JCML), a myeloproliferative disorder ;of childhood, is distinct from adult-type chronic myelogenous leukemia (CML) ;and bears resemblance to chronic myelomonocytic leukemia (CMMoL). ;[267..304]:malignancy:"Juvenile chronic myelogenous leukemia" ;[306..310]:malignancy:"JCML" ;[375..414]:malignancy:"adult-type chronic myelogenous leukemia" ;[416..419]:malignancy:"CML" ;[447..478]:malignancy:"chronic myelomonocytic leukemia" ;[480..485]:malignancy:"CMMoL" (SENT (S (NP-SBJ (NP (NP (JJ:[267..275] Juvenile) (JJ:[276..283] chronic) (JJ:[284..295] myelogenous) (NN:[296..304] leukemia)) (NP (-LRB-:[305..306] -LRB-) (NN:[306..310] JCML) (-RRB-:[310..311] -RRB-))) (,:[311..312] ,) (NP (NP (DT:[313..314] a) (JJ:[315..333] myeloproliferative) (NN:[334..342] disorder)) (PP (IN:[343..345] of) (NP (NN:[347..356] childhood))))) (,:[356..357] ,) (VP (VP (VBZ:[358..360] is) (ADJP-PRD (JJ:[361..369] distinct) (PP (IN:[370..374] from) (NP (NML (JJ:[375..380] adult) (HYPH:[380..381] -) (NN:[381..385] type)) (NML (NML (JJ:[386..393] chronic) (JJ:[394..405] myelogenous) (NN:[406..414] leukemia)) (NML (-LRB-:[415..416] -LRB-) (NN:[416..419] CML) (-RRB-:[419..420] -RRB-))))))) (CC:[421..424] and) (VP (VBZ:[426..431] bears) (NP (NP (NN:[432..443] resemblance)) (PP (TO:[444..446] to) (NP (NP (JJ:[447..454] chronic) (JJ:[455..469] myelomonocytic) (NN:[470..478] leukemia)) (NP (-LRB-:[479..480] -LRB-) (NN:[480..485] CMMoL) (-RRB-:[485..486] -RRB-))))))) (.:[486..487] .))) ;sentence 5 Span:488..667 ;Since mutations in the N-ras gene have been found at high frequencies in ;CMMoL, but only rarely in CML, we analyzed mutations activating the N-ras ;gene in 20 patients with JCML. ;[512..517]:gene-rna:"N-ras" ;[562..567]:malignancy:"CMMoL" ;[589..592]:malignancy:"CML" ;[631..636]:gene-rna:"N-ras" ;[662..666]:malignancy:"JCML" (SENT (S (SBAR-ADV (IN:[488..493] Since) (S (NP-SBJ-3 (NP (NNS:[494..503] mutations)) (PP (IN:[504..506] in) (NP (DT:[508..511] the) (NN:[512..517] N-ras) (NN:[518..522] gene)))) (VP (VBP:[523..527] have) (VP (VBN:[528..532] been) (VP (VP (VBN:[533..538] found) (NP-3 (-NONE-:[538..538] *)) (PP=2 (IN:[539..541] at) (NP (JJ:[542..546] high) (NNS:[547..558] frequencies))) (PP=1 (IN:[559..561] in) (NP (NN:[562..567] CMMoL)))) (,:[567..568] ,) (CC:[569..572] but) (VP (ADVP (RB:[573..577] only) (RB:[578..584] rarely)) (PP=2 (-NONE-:[584..584] *NOT*)) (PP=1 (IN:[585..587] in) (NP (NN:[589..592] CML))))))))) (,:[592..593] ,) (NP-SBJ (PRP:[594..596] we)) (VP (VBD:[597..605] analyzed) (NP (NP (NNS:[606..615] mutations)) (VP (VBG:[616..626] activating) (NP (DT:[627..630] the) (NN:[631..636] N-ras) (NN:[637..641] gene)))) (PP (IN:[642..644] in) (NP (NP (CD:[645..647] 20) (NNS:[648..656] patients)) (PP (IN:[657..661] with) (NP (NN:[662..666] JCML)))))) (.:[666..667] .))) ;sentence 6 Span:669..894 ;We used the strategy for analysis of gene mutations based on in vitro DNA ;amplification by polymerase chain reaction (PCR) followed by single-strand ;conformation polymorphism (SSCP) analysis and/or direct sequence analysis. ;[761..771]:gene-protein:"polymerase" (SENT (S (NP-SBJ (PRP:[669..671] We)) (VP (VBD:[672..676] used) (NP (NP (NP (DT:[677..680] the) (NN:[681..689] strategy)) (PP (IN:[690..693] for) (NP (NP (NN:[694..702] analysis)) (PP (IN:[703..705] of) (NP (NN:[706..710] gene) (NNS:[711..720] mutations)))))) (VP (VBN:[721..726] based) (NP (-NONE-:[726..726] *)) (PP (IN:[727..729] on) (NP (NP (NP (NML (FW:[730..732] in) (FW:[733..738] vitro)) (NN:[739..742] DNA) (NN:[744..757] amplification)) (PP (IN:[758..760] by) (NP (NP (NN:[761..771] polymerase) (NN:[772..777] chain) (NN:[778..786] reaction)) (NP (-LRB-:[787..788] -LRB-) (NN:[788..791] PCR) (-RRB-:[791..792] -RRB-))))) (VP (VBN:[793..801] followed) (NP (-NONE-:[801..801] *)) (PP-LGS (IN:[802..804] by) (NP (NP (NML (NML (NML (JJ:[805..811] single) (HYPH:[811..812] -) (NN:[812..818] strand)) (NN:[820..832] conformation) (NN:[833..845] polymorphism)) (NML (-LRB-:[846..847] -LRB-) (NN:[847..851] SSCP) (-RRB-:[851..852] -RRB-))) (NN:[853..861] analysis)) (CC:[862..868] and/or) (NP (JJ:[869..875] direct) (NN:[876..884] sequence) (NN:[885..893] analysis)))))))))) (.:[893..894] .))) ;sentence 7 Span:896..1024 ;Nucleotide sequence analysis showed single nucleotide substitutions involving ; codons 12, 13, or 61 in six of 20 patients (30%). ;[932..963]:variation-type:"single nucleotide substitutions" ;[975..981]...[982..984]...[986..988]...[993..995]:variation-location:"codons" ;..."12"..."13"..."61" (SENT (S (NP-SBJ (NN:[896..906] Nucleotide) (NN:[907..915] sequence) (NN:[916..924] analysis)) (VP (VBD:[925..931] showed) (NP (NP (JJ:[932..938] single) (NN:[939..949] nucleotide) (NNS:[950..963] substitutions)) (VP (VBG:[964..973] involving) (NP (NP (NML-1 (NNS:[975..981] codons)) (CD:[982..984] 12)) (,:[984..985] ,) (NP (NML-1 (-NONE-:[985..985] *P*)) (CD:[986..988] 13)) (,:[988..989] ,) (CC:[990..992] or) (NP (NML-1 (-NONE-:[992..992] *P*)) (CD:[993..995] 61))))) (PP-LOC (IN:[996..998] in) (NP (NP (CD:[999..1002] six)) (PP (IN:[1003..1005] of) (NP (CD:[1006..1008] 20) (NNS:[1009..1017] patients))) (PRN (-LRB-:[1018..1019] -LRB-) (NP (CD:[1019..1021] 30) (NN:[1021..1022] %)) (-RRB-:[1022..1023] -RRB-))))) (.:[1023..1024] .))) ;sentence 8 Span:1025..1174 ;Four of six patients with mutations were in chronic phase and the other two ;in blast crisis, indicating no apparent correlation with disease stage. ;[1052..1061]:variation-event:"mutations" ;[1070..1083]:malignancy:"chronic phase" ;[1105..1117]:malignancy:"blast crisis" (SENT (S (S (NP-SBJ=2 (NP (CD:[1025..1029] Four)) (PP (IN:[1030..1032] of) (NP (NP (CD:[1033..1036] six) (NNS:[1037..1045] patients)) (PP (IN:[1046..1050] with) (NP (NNS:[1052..1061] mutations)))))) (VP (VBD:[1062..1066] were) (PP-PRD=1 (IN:[1067..1069] in) (NP (JJ:[1070..1077] chronic) (NN:[1078..1083] phase))))) (CC:[1084..1087] and) (S (NP-SBJ=2 (DT:[1088..1091] the) (JJ:[1092..1097] other) (CD:[1098..1101] two)) (VP (PP-PRD=1 (IN:[1102..1104] in) (NP (NN:[1105..1110] blast) (NN:[1111..1117] crisis))) (,:[1117..1118] ,) (S-ADV (NP-SBJ (-NONE-:[1118..1118] *)) (VP (VBG:[1119..1129] indicating) (NP (NP (DT:[1130..1132] no) (JJ:[1134..1142] apparent) (NN:[1143..1154] correlation)) (PP (IN:[1155..1159] with) (NP (NN:[1160..1167] disease) (NN:[1168..1173] stage)))))))) (.:[1173..1174] .))) ;sentence 9 Span:1175..1335 ;Most of the patients with mutations were in the older age group with poor ;prognosis, although one patient in the younger age group also harbored the ;mutation. ;[1201..1210]:variation-event:"mutations" ;[1326..1334]:variation-event:"mutation" (SENT (S (NP-SBJ (NP (JJS:[1175..1179] Most)) (PP (IN:[1180..1182] of) (NP (NP (DT:[1183..1186] the) (NNS:[1187..1195] patients)) (PP (IN:[1196..1200] with) (NP (NNS:[1201..1210] mutations)))))) (VP (VBD:[1212..1216] were) (PP-PRD (IN:[1217..1219] in) (NP (NP (DT:[1220..1223] the) (JJR:[1224..1229] older) (NN:[1230..1233] age) (NN:[1234..1239] group)) (PP (IN:[1240..1244] with) (NP (JJ:[1245..1249] poor) (NN:[1250..1259] prognosis))))) (,:[1259..1260] ,) (SBAR (IN:[1261..1269] although) (S (NP-SBJ (NP (CD:[1270..1273] one) (NN:[1274..1281] patient)) (PP (IN:[1282..1284] in) (NP (DT:[1285..1288] the) (JJR:[1290..1297] younger) (NN:[1298..1301] age) (NN:[1302..1307] group)))) (ADVP (RB:[1308..1312] also)) (VP (VBD:[1313..1321] harbored) (NP (DT:[1322..1325] the) (NN:[1326..1334] mutation)))))) (.:[1334..1335] .))) ;sentence 10 Span:1336..1514 ;These data suggest that N-ras gene mutations may be involved in the ;pathogenesis and/or prognosis of JCML and provide further evidence that JCML ;is an entity distinct from CML. ;[1360..1365]:gene-rna:"N-ras" ;[1438..1442]:malignancy:"JCML" ;[1478..1482]:malignancy:"JCML" ;[1510..1513]:malignancy:"CML" (SENT (S (NP-SBJ (DT:[1336..1341] These) (NNS:[1342..1346] data)) (VP (VP (VBP:[1347..1354] suggest) (SBAR (IN:[1355..1359] that) (S (NP-SBJ-1 (NN:[1360..1365] N-ras) (NN:[1366..1370] gene) (NNS:[1372..1381] mutations)) (VP (MD:[1382..1385] may) (VP (VB:[1386..1388] be) (VP (VBN:[1389..1397] involved) (NP-1 (-NONE-:[1397..1397] *)) (PP-CLR (IN:[1398..1400] in) (NP (NP (DT:[1401..1404] the) (NN:[1405..1417] pathogenesis) (CC:[1418..1424] and/or) (NN:[1425..1434] prognosis)) (PP (IN:[1435..1437] of) (NP (NN:[1438..1442] JCML))))))))))) (CC:[1443..1446] and) (VP (VBP:[1448..1455] provide) (NP (JJ:[1456..1463] further) (NN:[1464..1472] evidence) (SBAR (IN:[1473..1477] that) (S (NP-SBJ (NN:[1478..1482] JCML)) (VP (VBZ:[1483..1485] is) (NP-PRD (NP (DT:[1486..1488] an) (NN:[1489..1495] entity)) (ADJP (JJ:[1496..1504] distinct) (PP (IN:[1505..1509] from) (NP (NN:[1510..1513] CML))))))))))) (.:[1513..1514] .))) ;section 11 Span:1518..1562 ;PMID: 8161790 [PubMed - indexed for MEDLINE] (SEC (FRAG (NNP:[1518..1522] PMID) (::[1522..1523] :) (CD:[1524..1531] 8161790) (NN:[1532..1533] -LSB-) (NNP:[1533..1539] PubMed) (::[1540..1541] -) (NN:[1542..1549] indexed) (IN:[1550..1553] for) (NNP:[1554..1562] MEDLINE-RSB-)))