;PMID: 2657575 ;source_file_1241.mrg ;Release 0.9 of PennBioIE ;Funded by NSF ITR EIA-0205448 ;0)section:[e:0..30] = [t:0..30] ;1)sentence:[e:35..90] = [t:35..90] ;2)section:[e:94..130] = [t:94..130] ;3)section:[e:134..236] = [t:134..236] ;4)sentence:[e:240..412] = [t:240..412] ;5)sentence:[e:413..578] = [t:413..578] ;6)sentence:[e:579..629] = [t:579..629] ;7)sentence:[e:630..823] = [t:630..823] ;8)sentence:[e:824..929] = [t:824..929] ;9)sentence:[e:930..1164] = [t:930..1164] ;10)sentence:[e:1165..1381] = [t:1165..1381] ;11)sentence:[e:1382..1657] = [t:1382..1657] ;12)section:[e:1661..1705] = [t:1661..1705] ;section 0 Span:0..30 ;Oncogene 1989 May;4(5):609-14 (SEC (FRAG (IN:[0..8] Oncogene) (CD:[10..14] 1989) (NNP:[15..18] May) (CD:[18..21] ;4-LRB-) (CD:[21..22] 5) (-RRB-:[22..23] -RRB-) (CD:[23..27] :609) (::[27..28] -) (CD:[28..30] 14))) ;sentence 1 Span:35..90 ;Mechanisms of ras mutation in myelodysplastic syndrome. ;[49..52]:gene-rna:"ras" ;[65..89]:malignancy:"myelodysplastic syndrome" (SENT (NP-HLN (NP (NNS:[35..45] Mechanisms)) (PP (IN:[46..48] of) (NP (NN:[49..52] ras) (NN:[53..61] mutation))) (PP (IN:[62..64] in) (NP (JJ:[65..80] myelodysplastic) (NN:[81..89] syndrome))) (.:[89..90] .))) ;section 2 Span:94..130 ;Yunis JJ, Boot AJ, Mayer MG, Bos JL. (SEC (FRAG (NNP:[94..99] Yunis) (NNP:[100..102] JJ) (,:[102..103] ,) (NNP:[104..108] Boot) (NNP:[109..111] AJ) (,:[111..112] ,) (NNP:[113..118] Mayer) (NNP:[119..121] MG) (,:[121..122] ,) (NNP:[123..126] Bos) (NNP:[127..130] JL.))) ;section 3 Span:134..236 ;Department of Laboratory Medicine and Pathology, University of Minnesota ;Medical School, Minneapolis. (SEC (FRAG (NNP:[134..144] Department) (IN:[145..147] of) (NNP:[148..158] Laboratory) (NNP:[159..167] Medicine) (CC:[168..171] and) (NNP:[172..181] Pathology) (,:[181..182] ,) (NNP:[183..193] University) (IN:[194..196] of) (NNP:[197..206] Minnesota) (NNP:[207..214] Medical) (NNP:[216..222] School) (,:[222..223] ,) (NNP:[224..235] Minneapolis) (.:[235..236] .))) ;sentence 4 Span:240..412 ;Using synthetic oligonucleotide hybridization, we have found a ras mutation ;in 11 of 27 patients (41%) with primary or non-therapy related ;myelodysplastic syndrome (MDS). ;[303..306]:gene-rna:"ras" ;[380..405]:malignancy:"myelodysplastic syndrome" ;[407..410]:malignancy:"MDS" (SENT (S (S-MNR (NP-SBJ (-NONE-:[240..240] *)) (VP (VBG:[240..245] Using) (NP (JJ:[246..255] synthetic) (NN:[256..271] oligonucleotide) (NN:[272..285] hybridization)))) (,:[285..286] ,) (NP-SBJ (PRP:[287..289] we)) (VP (VBP:[290..294] have) (VP (VBN:[295..300] found) (NP (DT:[301..302] a) (NN:[303..306] ras) (NN:[307..315] mutation)) (PP-LOC (IN:[316..318] in) (NP (NP (CD:[320..322] 11)) (PP (IN:[323..325] of) (NP (NP (CD:[326..328] 27) (NNS:[329..337] patients) (PRN (-LRB-:[338..339] -LRB-) (NP (CD:[339..341] 41) (NN:[341..342] %)) (-RRB-:[342..343] -RRB-))) (PP (IN:[344..348] with) (NP (NP (JJ:[349..356] primary) (NML-1 (-NONE-:[356..356] *P*))) (CC:[357..359] or) (NP (ADJP (AFX:[360..363] non) (HYPH:[363..364] -) (ADJP (NN:[364..371] therapy) (VBN:[372..379] related))) (NML-1 (NML (JJ:[380..395] myelodysplastic) (NN:[397..405] syndrome)) (NML (-LRB-:[406..407] -LRB-) (NN:[407..410] MDS) (-RRB-:[410..411] -RRB-)))))))))))) (.:[411..412] .))) ;sentence 5 Span:413..578 ;This high incidence of mutation, mainly of the N-ras oncogene, was generally ;found in patients with disease progression to acute leukemia (8 of 11 ;patients = 73%). ;[460..465]:gene-rna:"N-ras" ;[537..551]:malignancy:"acute leukemia" (SENT (S (NP-SBJ-1 (NP (DT:[413..417] This) (JJ:[418..422] high) (NN:[423..432] incidence)) (PP (IN:[433..435] of) (NP (NN:[436..444] mutation)))) (,:[444..445] ,) (PP (ADVP (RB:[446..452] mainly)) (IN:[453..455] of) (NP (DT:[456..459] the) (NN:[460..465] N-ras) (NN:[466..474] oncogene))) (,:[474..475] ,) (VP (VBD:[477..480] was) (ADVP (RB:[481..490] generally)) (VP (VBN:[491..496] found) (NP-1 (-NONE-:[496..496] *)) (PP-LOC (IN:[497..499] in) (NP (NP (NNS:[500..508] patients)) (PP (IN:[509..513] with) (NP (NP (NN:[514..521] disease) (NN:[522..533] progression)) (PP (TO:[534..536] to) (NP (JJ:[537..542] acute) (NN:[543..551] leukemia))))))) (PRN (-LRB-:[552..553] -LRB-) (S (NP-SBJ (NP (CD:[553..554] 8)) (PP (IN:[555..557] of) (NP (CD:[559..561] 11) (NNS:[562..570] patients)))) (VP (SYM:[571..572] =) (NP (CD:[573..575] 73) (NN:[575..576] %)))) (-RRB-:[576..577] -RRB-)))) (.:[577..578] .))) ;sentence 6 Span:579..629 ;Two general mechanisms of ras mutation were found. ;[605..608]:gene-rna:"ras" (SENT (S (NP-SBJ-1 (NP (CD:[579..582] Two) (JJ:[583..590] general) (NNS:[591..601] mechanisms)) (PP (IN:[602..604] of) (NP (NN:[605..608] ras) (NN:[609..617] mutation)))) (VP (VBD:[618..622] were) (VP (VBN:[623..628] found) (NP-1 (-NONE-:[628..628] *)))) (.:[628..629] .))) ;sentence 7 Span:630..823 ;In five patients the ras mutation was present in only a fraction of the ;cells; sometimes appearing in late stages of the disease, suggesting that it ;can occur in a differentiated cell clone. ;[652..655]:gene-rna:"ras" ;[734..760]:malignancy:"late stages of the disease" (SENT (S (PP (IN:[630..632] In) (NP (CD:[633..637] five) (NNS:[639..647] patients))) (NP-SBJ (DT:[648..651] the) (NN:[652..655] ras) (NN:[656..664] mutation)) (VP (VBD:[665..668] was) (ADJP-PRD (JJ:[669..676] present) (PP (IN:[677..679] in) (NP (NP (ADVP (RB:[680..684] only)) (DT:[685..686] a) (NN:[687..695] fraction)) (PP (IN:[696..698] of) (NP (DT:[699..702] the) (NNS:[703..708] cells)))))) (::[708..709] ;) (S-ADV (NP-SBJ (-NONE-:[709..709] *)) (ADVP-TMP (RB:[710..719] sometimes)) (VP (VBG:[721..730] appearing) (PP (IN:[731..733] in) (NP (NP (JJ:[734..738] late) (NNS:[739..745] stages)) (PP (IN:[746..748] of) (NP (DT:[749..752] the) (NN:[753..760] disease))))))) (,:[760..761] ,) (S-ADV (NP-SBJ (-NONE-:[761..761] *)) (VP (VBG:[762..772] suggesting) (SBAR (IN:[773..777] that) (S (NP-SBJ (PRP:[778..780] it)) (VP (MD:[781..784] can) (VP (VB:[785..790] occur) (PP-LOC (IN:[791..793] in) (NP (DT:[794..795] a) (VBN:[797..811] differentiated) (NN:[812..816] cell) (NN:[817..822] clone)))))))))) (.:[822..823] .))) ;sentence 8 Span:824..929 ;In six other patients, the ras mutation was present in the great majority of ;bone marrow or blood cells. ;[851..854]:gene-rna:"ras" (SENT (S (PP (IN:[824..826] In) (NP (CD:[827..830] six) (JJ:[831..836] other) (NNS:[837..845] patients))) (,:[845..846] ,) (NP-SBJ (DT:[847..850] the) (NN:[851..854] ras) (NN:[855..863] mutation)) (VP (VBD:[864..867] was) (ADJP-PRD (JJ:[868..875] present) (PP (IN:[877..879] in) (NP (NP (DT:[880..883] the) (JJ:[884..889] great) (NN:[890..898] majority)) (PP (IN:[899..901] of) (NP (NP (NML (NN:[902..906] bone) (NN:[907..913] marrow)) (NML-1 (-NONE-:[913..913] *P*))) (CC:[914..916] or) (NP (NN:[917..922] blood) (NML-1 (NNS:[923..928] cells))))))))) (.:[928..929] .))) ;sentence 9 Span:930..1164 ;The mutation was detected in mature normal lymphocytes and persisted ;following a complete clinical remission in two of these patients, implying ;that the ras mutation can occur in an early stage of cell differentiation or ;stem cell. ;[1085..1088]:gene-rna:"ras" (SENT (S (NP-SBJ-1 (DT:[930..933] The) (NN:[934..942] mutation)) (VP (VP (VBD:[943..946] was) (VP (VBN:[947..955] detected) (NP-1 (-NONE-:[955..955] *)) (PP-LOC (IN:[957..959] in) (NP (JJ:[960..966] mature) (JJ:[967..973] normal) (NNS:[974..985] lymphocytes))))) (CC:[986..989] and) (VP (VBD:[990..999] persisted) (PP (VBG:[1000..1009] following) (NP (DT:[1010..1011] a) (JJ:[1012..1020] complete) (JJ:[1021..1029] clinical) (NN:[1031..1040] remission))) (PP-LOC (IN:[1041..1043] in) (NP (NP (CD:[1044..1047] two)) (PP (IN:[1048..1050] of) (NP (DT:[1051..1056] these) (NNS:[1057..1065] patients))))) (,:[1065..1066] ,) (S-ADV (NP-SBJ (-NONE-:[1066..1066] *)) (VP (VBG:[1067..1075] implying) (SBAR (IN:[1076..1080] that) (S (NP-SBJ (DT:[1081..1084] the) (NN:[1085..1088] ras) (NN:[1089..1097] mutation)) (VP (MD:[1098..1101] can) (VP (VB:[1102..1107] occur) (PP (IN:[1108..1110] in) (NP (NP (DT:[1112..1114] an) (JJ:[1115..1120] early) (NN:[1121..1126] stage)) (PP (IN:[1127..1129] of) (NP (NP (NN:[1130..1134] cell) (NN:[1135..1150] differentiation)) (CC:[1151..1153] or) (NP (NN:[1154..1158] stem) (NN:[1159..1163] cell)))))))))))))) (.:[1163..1164] .))) ;sentence 10 Span:1165..1381 ;Patients with a ras mutation had a median survival of nine months (all ;patients dead) compared to 16 patients without a ras mutation that had a ;median follow-up of 16 months (10 patients alive; P less than 0.005). ;[1181..1184]:gene-rna:"ras" ;[1287..1290]:gene-rna:"ras" (SENT (S (NP-SBJ (NP (NNS:[1165..1173] Patients)) (PP (IN:[1174..1178] with) (NP (DT:[1179..1180] a) (NN:[1181..1184] ras) (NN:[1186..1194] mutation)))) (VP (VBD:[1195..1198] had) (NP (NP (DT:[1199..1200] a) (JJ:[1201..1207] median) (NN:[1208..1216] survival)) (PP (IN:[1217..1219] of) (NP (CD:[1220..1224] nine) (NNS:[1225..1231] months)))) (PRN (-LRB-:[1232..1233] -LRB-) (S (NP-SBJ (DT:[1233..1236] all) (NNS:[1237..1245] patients)) (ADJP-PRD (JJ:[1246..1250] dead))) (-RRB-:[1250..1251] -RRB-)) (S-ADV (NP-SBJ-2 (-NONE-:[1251..1251] *)) (VP (VBN:[1252..1260] compared) (NP-2 (-NONE-:[1260..1260] *)) (PP-CLR (TO:[1261..1263] to) (NP (NP (NP (CD:[1264..1266] 16) (NNS:[1268..1276] patients)) (PP (IN:[1277..1284] without) (NP (DT:[1285..1286] a) (NN:[1287..1290] ras) (NN:[1291..1299] mutation)))) (SBAR (WHNP-1 (WDT:[1300..1304] that)) (S (NP-SBJ-1 (-NONE-:[1304..1304] *T*)) (VP (VBD:[1305..1308] had) (NP (NP (DT:[1309..1310] a) (JJ:[1311..1317] median) (VB:[1318..1324] follow) (HYPH:[1324..1325] -) (RP:[1325..1327] up)) (PP (IN:[1328..1330] of) (NP (CD:[1331..1333] 16) (NNS:[1334..1340] months)))) (PRN (-LRB-:[1341..1342] -LRB-) (FRAG (S (NP-SBJ (CD:[1342..1344] 10) (NNS:[1346..1354] patients)) (ADJP-PRD (JJ:[1355..1360] alive))) (::[1360..1361] ;) (S (NP-SBJ (NN:[1362..1363] P)) (ADJP-PRD (ADJP (JJR:[1364..1368] less)) (PP (IN:[1369..1373] than) (NP (CD:[1374..1379] 0.005)))))) (-RRB-:[1379..1380] -RRB-)))))))))) (.:[1380..1381] .))) ;sentence 11 Span:1382..1657 ;Since 9 of the 11 patients (82%) with a ras mutation were found to have an ;abnormal monocytic component at diagnosis or during disease evolution, it is ;possible that in myeloid disorders a ras mutation is preferentially ;associated with myelomonocytic cell differentiation. ;[1422..1425]:gene-rna:"ras" ;[1553..1570]:malignancy:"myeloid disorders" ;[1573..1576]:gene-rna:"ras" (SENT (S (SBAR-ADV (IN:[1382..1387] Since) (S (NP-SBJ-1 (NP (CD:[1388..1389] 9)) (PP (IN:[1390..1392] of) (NP (NP (DT:[1393..1396] the) (CD:[1397..1399] 11) (NNS:[1400..1408] patients) (PRN (-LRB-:[1409..1410] -LRB-) (NP (CD:[1410..1412] 82) (NN:[1412..1413] %)) (-RRB-:[1413..1414] -RRB-))) (PP (IN:[1415..1419] with) (NP (DT:[1420..1421] a) (NN:[1422..1425] ras) (NN:[1427..1435] mutation)))))) (VP (VBD:[1436..1440] were) (VP (VBN:[1441..1446] found) (S (NP-SBJ-1 (-NONE-:[1446..1446] *)) (VP (TO:[1447..1449] to) (VP (VB:[1450..1454] have) (NP (DT:[1455..1457] an) (JJ:[1458..1466] abnormal) (JJ:[1467..1476] monocytic) (NN:[1477..1486] component)) (PP-TMP (PP (IN:[1487..1489] at) (NP (NN:[1490..1499] diagnosis))) (CC:[1500..1502] or) (PP (IN:[1504..1510] during) (NP (NN:[1511..1518] disease) (NN:[1519..1528] evolution))))))))))) (,:[1528..1529] ,) (NP-SBJ (PRP:[1530..1532] it)) (VP (VBZ:[1533..1535] is) (ADJP-PRD (JJ:[1536..1544] possible) (SBAR (IN:[1545..1549] that) (S (PP (IN:[1550..1552] in) (NP (JJ:[1553..1560] myeloid) (NNS:[1561..1570] disorders))) (NP-SBJ (DT:[1571..1572] a) (NN:[1573..1576] ras) (NN:[1578..1586] mutation)) (VP (VBZ:[1587..1589] is) (ADVP (RB:[1590..1604] preferentially)) (VP (VBN:[1605..1615] associated) (PP-CLR (IN:[1616..1620] with) (NP (JJ:[1621..1635] myelomonocytic) (NN:[1636..1640] cell) (NN:[1641..1656] differentiation))))))))) (.:[1656..1657] .))) ;section 12 Span:1661..1705 ;PMID: 2657575 [PubMed - indexed for MEDLINE] (SEC (FRAG (NNP:[1661..1665] PMID) (::[1665..1666] :) (CD:[1667..1674] 2657575) (NN:[1675..1676] -LSB-) (NNP:[1676..1682] PubMed) (::[1683..1684] -) (NN:[1685..1692] indexed) (IN:[1693..1696] for) (NNP:[1697..1705] MEDLINE-RSB-)))