;PMID: 8483882 ;source_file_1228.mrg ;Release 0.9 of PennBioIE ;Funded by NSF ITR EIA-0205448 ;0)section:[e:0..32] = [t:0..32] ;1)sentence:[e:37..85] = [t:37..85] ;2)section:[e:89..120] = [t:89..120] ;3)section:[e:124..179] = [t:124..179] ;4)sentence:[e:183..292] = [t:183..292] ;5)sentence:[e:293..384] = [t:293..384] ;6)sentence:[e:385..696] = [t:385..696] ;7)sentence:[e:697..893] = [t:697..893] ;8)sentence:[e:894..1045] = [t:894..1045] ;9)sentence:[e:1046..1174] = [t:1046..1174] ;10)sentence:[e:1175..1239] = [t:1175..1239] ;11)sentence:[e:1240..1347] = [t:1240..1347] ;12)sentence:[e:1348..1464] = [t:1348..1464] ;13)sentence:[e:1465..1589] = [t:1465..1589] ;14)sentence:[e:1591..1803] = [t:1591..1803] ;15)section:[e:1807..1851] = [t:1807..1851] ;section 0 Span:0..32 ;Mod Pathol 1993 Mar;6(2):129-32 (SEC (FRAG (NNP:[0..3] Mod) (NNP:[4..10] Pathol) (CD:[12..16] 1993) (CC:[17..23] Mar;6-LRB-) (CD:[23..24] 2) (-RRB-:[24..25] -RRB-) (CD:[25..29] :129) (::[29..30] -) (CD:[30..32] 32))) ;sentence 1 Span:37..85 ;H-ras-1 point mutations in soft tissue sarcomas. ;[37..44]:gene-rna:"H-ras-1" ;[45..60]:variation-type:"point mutations" ;[64..84]:malignancy:"soft tissue sarcomas" (SENT (NP-HLN (NP (NN:[37..44] H-ras-1) (NN:[45..50] point) (NNS:[51..60] mutations)) (PP (IN:[61..63] in) (NP (NML (JJ:[64..68] soft) (NN:[69..75] tissue)) (NNS:[76..84] sarcomas))) (.:[84..85] .))) ;section 2 Span:89..120 ;Wilke W, Maillet M, Robinson R. (SEC (FRAG (NNP:[89..94] Wilke) (NNP:[95..96] W) (,:[96..97] ,) (NNP:[98..105] Maillet) (NNP:[106..108] M,) (NNP:[109..117] Robinson) (NNP:[118..120] R.))) ;section 3 Span:124..179 ;Department of Pathology, University of Iowa, Iowa City. (SEC (FRAG (NNP:[124..134] Department) (IN:[135..137] of) (NNP:[138..147] Pathology) (,:[147..148] ,) (NNP:[149..159] University) (IN:[160..162] of) (NNP:[163..167] Iowa) (,:[167..168] ,) (NNP:[169..173] Iowa) (NNP:[174..178] City) (.:[178..179] .))) ;sentence 4 Span:183..292 ;The H-ras-1 protooncogene is activated by single base substitutions occurring ;in either codon 12, 13, or 61. ;[187..194]:gene-rna:"H-ras-1" ;[225..250]:variation-type:"single base substitutions" ;[272..280]:variation-location:"codon 12" ;[272..277]...[289..291]:variation-location:"codon"..."61" ;[272..277]...[282..284]:variation-location:"codon"..."13" (SENT (S (NP-SBJ-1 (DT:[183..186] The) (NN:[187..194] H-ras-1) (NN:[195..208] protooncogene)) (VP (VBZ:[209..211] is) (VP (VBN:[212..221] activated) (NP-1 (-NONE-:[221..221] *)) (PP (IN:[222..224] by) (NP-LGS (NP (NML (JJ:[225..231] single) (NN:[232..236] base)) (NNS:[237..250] substitutions)) (VP (VBG:[251..260] occurring) (PP-LOC (IN:[261..263] in) (NP (CC:[265..271] either) (NP (NML-2 (NN:[272..277] codon)) (CD:[278..280] 12)) (,:[280..281] ,) (NP (NML-2 (-NONE-:[281..281] *P*)) (CD:[282..284] 13)) (,:[284..285] ,) (CC:[286..288] or) (NP (NML-2 (-NONE-:[288..288] *P*)) (CD:[289..291] 61))))))))) (.:[291..292] .))) ;sentence 5 Span:293..384 ;These mutations have been described with varying frequencies in several ;human tumor types. ;[299..308]:variation-event:"mutations" (SENT (S (NP-SBJ-1 (DT:[293..298] These) (NNS:[299..308] mutations)) (VP (VBP:[309..313] have) (VP (VBN:[314..318] been) (VP (VBN:[319..328] described) (NP-1 (-NONE-:[328..328] *)) (PP (IN:[329..333] with) (NP (NP (VBG:[334..341] varying) (NNS:[343..354] frequencies)) (PP (IN:[355..357] in) (NP (JJ:[358..365] several) (JJ:[366..371] human) (NN:[372..377] tumor) (NNS:[378..383] types)))))))) (.:[383..384] .))) ;sentence 6 Span:385..696 ;Since ras oncogenes were first discovered as the transforming sequences of ;Harvey and Kirsten murine sarcoma viruses (which also contain activating ;point mutations compared to the homologous cellular sequences), we wished to ;investigate the possibility that ras mutations might also occur in human ;sarcomas. ;[391..394]:gene-rna:"ras" ;[535..550]:variation-type:"point mutations" ;[647..650]:gene-rna:"ras" ;[687..695]:malignancy:"sarcomas" (SENT (S (SBAR-PRP (IN:[385..390] Since) (S (NP-SBJ-1 (NN:[391..394] ras) (NNS:[395..404] oncogenes)) (VP (VBD:[405..409] were) (VP (ADVP (RB:[410..415] first)) (VBN:[417..427] discovered) (NP-1 (-NONE-:[427..427] *)) (PP (IN:[428..430] as) (NP (NP (NP (DT:[431..434] the) (VBG:[435..447] transforming) (NNS:[448..457] sequences)) (PP (IN:[458..460] of) (NP (NP (NML (NNP:[461..467] Harvey) (CC:[468..471] and) (NNP:[472..479] Kirsten)) (JJ:[480..486] murine) (NN:[487..494] sarcoma) (NNS:[496..503] viruses)) (-LRB-:[504..505] -LRB-)))) (SBAR (WHNP-2 (WDT:[505..510] which)) (S (NP-SBJ-2 (-NONE-:[510..510] *T*)) (VP (ADVP (RB:[511..515] also)) (VBP:[516..523] contain) (NP (NP (VBG:[524..534] activating) (NN:[535..540] point) (NNS:[541..550] mutations)) (VP (VBN:[551..559] compared) (NP (-NONE-:[559..559] *)) (PP-CLR (TO:[560..562] to) (NP (DT:[563..566] the) (JJ:[568..578] homologous) (JJ:[579..587] cellular) (NNS:[588..597] sequences))) (-RRB-:[597..598] -RRB-)))))))))))) (,:[598..599] ,) (NP-SBJ (PRP:[600..602] we)) (VP (VBD:[603..609] wished) (S (NP-SBJ (-NONE-:[609..609] *)) (VP (TO:[610..612] to) (VP (VB:[613..624] investigate) (NP (NP (DT:[625..628] the) (NN:[629..640] possibility)) (SBAR (IN:[641..645] that) (S (NP-SBJ (NN:[647..650] ras) (NNS:[651..660] mutations)) (VP (MD:[661..666] might) (ADVP (RB:[667..671] also)) (VP (VB:[672..677] occur) (PP-LOC (IN:[678..680] in) (NP (JJ:[681..686] human) (NNS:[687..695] sarcomas)))))))))))) (.:[695..696] .))) ;sentence 7 Span:697..893 ;We extracted DNA from six malignant fibrous histiocytomas (MFH), three ;embryonal rhabdomyosarcomas (ER), one alveolar rhabdomyosarcoma, one ;pleomorphic rhabdomyosarcoma, and one leiomyosarcoma. ;[724..755]:malignancy:"malignant fibrous histiocytomas" ;[757..760]:malignancy:"MFH" ;[769..796]:malignancy:"embryonal rhabdomyosarcomas" ;[798..800]:malignancy:"ER" ;[808..833]:malignancy:"alveolar rhabdomyosarcoma" ;[839..867]:malignancy:"pleomorphic rhabdomyosarcoma" ;[878..892]:malignancy:"leiomyosarcoma" (SENT (S (NP-SBJ (PRP:[697..699] We)) (VP (VBD:[700..709] extracted) (NP (NN:[710..713] DNA)) (PP (IN:[714..718] from) (NP (NP (CD:[719..722] six) (NML (NML (JJ:[724..733] malignant) (JJ:[734..741] fibrous) (NNS:[742..755] histiocytomas)) (NML (-LRB-:[756..757] -LRB-) (NN:[757..760] MFH) (-RRB-:[760..761] -RRB-)))) (,:[761..762] ,) (NP (CD:[763..768] three) (NML (NML (JJ:[769..778] embryonal) (NNS:[779..796] rhabdomyosarcomas)) (NML (-LRB-:[797..798] -LRB-) (NN:[798..800] ER) (-RRB-:[800..801] -RRB-)))) (,:[801..802] ,) (NP (CD:[804..807] one) (JJ:[808..816] alveolar) (NN:[817..833] rhabdomyosarcoma)) (,:[833..834] ,) (NP (CD:[835..838] one) (JJ:[839..850] pleomorphic) (NN:[851..867] rhabdomyosarcoma)) (,:[867..868] ,) (CC:[869..872] and) (NP (CD:[873..876] one) (NN:[878..892] leiomyosarcoma))))) (.:[892..893] .))) ;sentence 8 Span:894..1045 ;The DNA from regions flanking codons 12/13 and codon 61 was amplified by the ;polymerase chain reaction and sequenced with an automated DNA sequencer. ;[907..936]:variation-location:"regions flanking codons 12/13" ;[941..949]:variation-location:"codon 61" ;[972..982]:gene-protein:"polymerase" (SENT (S (NP-SBJ-1 (NP (DT:[894..897] The) (NN:[898..901] DNA)) (PP (IN:[902..906] from) (NP (NP (NNS:[907..914] regions)) (VP (VBG:[915..923] flanking) (NP (NP (NP (NML-2 (NNS:[924..930] codons)) (CD:[931..933] 12)) (SYM:[933..934] /) (NP (NML-2 (-NONE-:[934..934] *P*)) (NP (CD:[934..936] 13)))) (CC:[937..940] and) (NP (NN:[941..946] codon) (CD:[947..949] 61))))))) (VP (VBD:[950..953] was) (VP (VP (VBN:[955..964] amplified) (NP-1 (-NONE-:[964..964] *)) (PP-MNR (IN:[965..967] by) (NP (DT:[968..971] the) (NN:[972..982] polymerase) (NN:[983..988] chain) (NN:[989..997] reaction)))) (CC:[998..1001] and) (VP (VBN:[1002..1011] sequenced) (NP-1 (-NONE-:[1011..1011] *)) (PP-MNR (IN:[1012..1016] with) (NP (DT:[1017..1019] an) (VBN:[1020..1029] automated) (NN:[1030..1033] DNA) (NN:[1035..1044] sequencer)))))) (.:[1044..1045] .))) ;sentence 9 Span:1046..1174 ;As controls, we amplified and sequenced normal DNA (placenta) and DNA with ;known point mutations (T24 bladder carcinoma cells). ;[1128..1143]:variation-type:"point mutations" ;[1145..1172]:malignancy:"T24 bladder carcinoma cells" (SENT (S (PP (IN:[1046..1048] As) (NP (NNS:[1049..1057] controls))) (,:[1057..1058] ,) (NP-SBJ (PRP:[1059..1061] we)) (VP (VBD:[1062..1071] amplified) (CC:[1072..1075] and) (VBD:[1076..1085] sequenced) (NP (NP (JJ:[1086..1092] normal) (NN:[1093..1096] DNA) (PRN (-LRB-:[1097..1098] -LRB-) (NP (NN:[1098..1106] placenta)) (-RRB-:[1106..1107] -RRB-))) (CC:[1108..1111] and) (NP (NP (NN:[1112..1115] DNA)) (PP (IN:[1117..1121] with) (NP (VBN:[1122..1127] known) (NN:[1128..1133] point) (NNS:[1134..1143] mutations) (PRN (-LRB-:[1144..1145] -LRB-) (NP (NN:[1145..1148] T24) (NN:[1149..1156] bladder) (NN:[1157..1166] carcinoma) (NNS:[1167..1172] cells)) (-RRB-:[1172..1173] -RRB-))))))) (.:[1173..1174] .))) ;sentence 10 Span:1175..1239 ;We found three cases with mutations, all occurring in codon 12. ;[1202..1211]:variation-event:"mutations" ;[1230..1238]:variation-location:"codon 12" (SENT (S (S (NP-SBJ (PRP:[1175..1177] We)) (VP (VBD:[1178..1183] found) (NP (NP (CD:[1184..1189] three) (NNS:[1190..1195] cases)) (PP (IN:[1197..1201] with) (NP (NNS:[1202..1211] mutations)))))) (,:[1211..1212] ,) (S (NP-SBJ (DT:[1213..1216] all)) (VP (VBG:[1217..1226] occurring) (PP-LOC (IN:[1227..1229] in) (NP (NN:[1230..1235] codon) (CD:[1236..1238] 12))))) (.:[1238..1239] .))) ;sentence 11 Span:1240..1347 ;One ER showed a G-to-T mutation in the second position of codon 12 (coding ;for valine instead of glycine). ;[1244..1246]:malignancy:"ER" ;[1256..1257]:variation-state-original:"G" ;[1261..1262]:variation-state-altered:"T" ;[1263..1271]:variation-event:"mutation" ;[1280..1307]:variation-location:"second position of codon 12" ;[1320..1326]:variation-state-altered:"valine" ;[1338..1345]:variation-state-original:"glycine" (SENT (S (NP-SBJ (CD:[1240..1243] One) (NN:[1244..1246] ER)) (VP (VBD:[1247..1253] showed) (NP (DT:[1254..1255] a) (NML (NML (NN:[1256..1257] G) (HYPH:[1257..1258] -)) (PP (TO:[1258..1260] to) (HYPH:[1260..1261] -) (NP (NN:[1261..1262] T)))) (NN:[1263..1271] mutation)) (PP-LOC (IN:[1272..1274] in) (NP (NP (DT:[1276..1279] the) (JJ:[1280..1286] second) (NN:[1287..1295] position)) (PP (IN:[1296..1298] of) (NP (NN:[1299..1304] codon) (CD:[1305..1307] 12))) (PRN (-LRB-:[1308..1309] -LRB-) (VP (VBG:[1309..1315] coding) (PP (IN:[1316..1319] for) (NP (NN:[1320..1326] valine))) (ADVP (RB:[1327..1334] instead) (PP (IN:[1335..1337] of) (NP (NN:[1338..1345] glycine))))) (-RRB-:[1345..1346] -RRB-))))) (.:[1346..1347] .))) ;sentence 12 Span:1348..1464 ;Two MFHs showed G-to-A mutations in the second position of codon 12 (coding ;for aspartic acid instead of glycine). ;[1352..1356]:malignancy:"MFHs" ;[1365..1366]:variation-state-original:"G" ;[1370..1371]:variation-state-altered:"A" ;[1372..1381]:variation-event:"mutations" ;[1389..1416]:variation-location:"second position of codon 12" ;[1429..1437]:variation-state-altered:"aspartic" ;[1455..1462]:variation-state-original:"glycine" (SENT (S (NP-SBJ (CD:[1348..1351] Two) (NNS:[1352..1356] MFHs)) (VP (VBD:[1358..1364] showed) (NP (NP (NML (NML (NN:[1365..1366] G) (HYPH:[1366..1367] -)) (PP (TO:[1367..1369] to) (HYPH:[1369..1370] -) (NP (NN:[1370..1371] A)))) (NNS:[1372..1381] mutations)) (PP-LOC (IN:[1382..1384] in) (NP (NP (DT:[1385..1388] the) (JJ:[1389..1395] second) (NN:[1396..1404] position)) (PP (IN:[1405..1407] of) (NP (NN:[1408..1413] codon) (CD:[1414..1416] 12))) (PRN (-LRB-:[1417..1418] -LRB-) (VP (VBG:[1418..1424] coding) (PP (IN:[1425..1428] for) (NP (JJ:[1429..1437] aspartic) (NN:[1439..1443] acid))) (ADVP (RB:[1444..1451] instead) (PP (IN:[1452..1454] of) (NP (NN:[1455..1462] glycine))))) (-RRB-:[1462..1463] -RRB-)))))) (.:[1463..1464] .))) ;sentence 13 Span:1465..1589 ;Although a limited number of cases were sampled, we conclude that study of ;H-ras-1 mutations may be relevant to MFH and ER. ;[1541..1548]:gene-rna:"H-ras-1" ;[1578..1581]:malignancy:"MFH" ;[1586..1588]:malignancy:"ER" (SENT (S (SBAR-ADV (IN:[1465..1473] Although) (S (NP-SBJ-1 (NP (DT:[1474..1475] a) (VBN:[1476..1483] limited) (NN:[1484..1490] number)) (PP (IN:[1491..1493] of) (NP (NNS:[1494..1499] cases)))) (VP (VBD:[1500..1504] were) (VP (VBN:[1505..1512] sampled) (NP-1 (-NONE-:[1512..1512] *)))))) (,:[1512..1513] ,) (NP-SBJ (PRP:[1514..1516] we)) (VP (VBP:[1518..1526] conclude) (SBAR (IN:[1527..1531] that) (S (NP-SBJ (NP (NN:[1532..1537] study)) (PP (IN:[1538..1540] of) (NP (NN:[1541..1548] H-ras-1) (NNS:[1549..1558] mutations)))) (VP (MD:[1559..1562] may) (VP (VB:[1563..1565] be) (ADJP-PRD (JJ:[1566..1574] relevant) (PP (TO:[1575..1577] to) (NP (NN:[1578..1581] MFH) (CC:[1582..1585] and) (NN:[1586..1588] ER))))))))) (.:[1588..1589] .))) ;sentence 14 Span:1591..1803 ;Additional studies of N and K-ras mutations as well as more cases ;investigating H-ras will be required before we can ascertain the ;significance of ras mutations in the oncogenesis of human soft tissue ;sarcomas. ;[1613..1614]...[1621..1624]:gene-rna:"N"..."ras" ;[1619..1624]:gene-rna:"K-ras" ;[1672..1677]:gene-rna:"H-ras" ;[1739..1742]:gene-rna:"ras" ;[1782..1802]:malignancy:"soft tissue sarcomas" (SENT (S (NP-SBJ-3 (NP (NP (JJ:[1591..1601] Additional) (NNS:[1602..1609] studies)) (PP (IN:[1610..1612] of) (NP (NP (NN:[1613..1614] N) (NML-1 (-NONE-:[1614..1614] *P*)) (NML-2 (-NONE-:[1614..1614] *P*))) (CC:[1615..1618] and) (NP (NN:[1619..1620] K) (HYPH:[1620..1621] -) (NML-1 (NN:[1621..1624] ras)) (NML-2 (NNS:[1625..1634] mutations)))))) (CONJP (RB:[1635..1637] as) (RB:[1638..1642] well) (IN:[1643..1645] as)) (NP (NP (JJR:[1646..1650] more) (NNS:[1651..1656] cases)) (VP (VBG:[1657..1670] investigating) (NP (NN:[1672..1677] H-ras))))) (VP (MD:[1678..1682] will) (VP (VB:[1683..1685] be) (VP (VBN:[1686..1694] required) (NP-3 (-NONE-:[1694..1694] *)) (SBAR-TMP (IN:[1695..1701] before) (S (NP-SBJ (PRP:[1702..1704] we)) (VP (MD:[1705..1708] can) (VP (VB:[1709..1718] ascertain) (NP (NP (DT:[1719..1722] the) (NN:[1723..1735] significance)) (PP (IN:[1736..1738] of) (NP (NP (NN:[1739..1742] ras) (NNS:[1743..1752] mutations)) (PP (IN:[1754..1756] in) (NP (NP (DT:[1757..1760] the) (NN:[1761..1772] oncogenesis)) (PP (IN:[1773..1775] of) (NP (JJ:[1776..1781] human) (NML (JJ:[1782..1786] soft) (NN:[1787..1793] tissue)) (NNS:[1794..1802] sarcomas))))))))))))))) (.:[1802..1803] .))) ;section 15 Span:1807..1851 ;PMID: 8483882 [PubMed - indexed for MEDLINE] (SEC (FRAG (NNP:[1807..1811] PMID) (::[1811..1812] :) (CD:[1813..1820] 8483882) (NN:[1821..1822] -LSB-) (NNP:[1822..1828] PubMed) (::[1829..1830] -) (NN:[1831..1838] indexed) (IN:[1839..1842] for) (NNP:[1843..1851] MEDLINE-RSB-)))