;PMID: 9738576 ;source_file_1398.mrg ;Release 0.9 of PennBioIE ;Funded by NSF ITR EIA-0205448 ;0)section:[e:0..35] = [t:0..35] ;1)sentence:[e:40..148] = [t:40..148] ;2)section:[e:152..206] = [t:152..206] ;3)section:[e:210..290] = [t:210..290] ;4)sentence:[e:294..302] = [t:294..302] ;5)sentence:[e:303..433] = [t:303..433] ;6)sentence:[e:434..634] = [t:434..634] ;7)sentence:[e:635..800] = [t:635..800] ;8)sentence:[e:801..822] = [t:801..822] ;9)sentence:[e:823..946] = [t:823..946] ;10)sentence:[e:947..1088] = [t:947..1088] ;11)sentence:[e:1089..1097] = [t:1089..1097] ;12)sentence:[e:1098..1186] = [t:1098..1186] ;13)sentence:[e:1187..1325] = [t:1187..1325] ;14)sentence:[e:1326..1431] = [t:1326..1431] ;15)sentence:[e:1432..1564] = [t:1432..1564] ;16)sentence:[e:1565..1686] = [t:1565..1686] ;17)sentence:[e:1687..1698] = [t:1687..1698] ;18)sentence:[e:1700..1831] = [t:1700..1831] ;19)sentence:[e:1832..1925] = [t:1832..1925] ;20)section:[e:1929..1973] = [t:1929..1973] ;section 0 Span:0..35 ;J Clin Oncol 1998 Sep;16(9):3061-8 (SEC (FRAG (NNP:[0..1] J) (DT:[2..6] Clin) (NNP:[7..12] Oncol) (CD:[14..18] 1998) (.:[19..27] Sep;16-LRB-9) (-RRB-:[27..28] -RRB-) (CD:[28..33] :3061) (::[33..34] -) (CD:[34..35] 8))) ;sentence 1 Span:40..148 ;Detection of K-ras point mutations in sputum from patients with ;adenocarcinoma of the lung by point-EXACCT. ;[53..58]:gene-rna:"K-ras" ;[59..74]:variation-type:"point mutations" ;[104..131]:malignancy:"adenocarcinoma of the lung" (SENT (NP-HLN (NP (NN:[40..49] Detection)) (PP (IN:[50..52] of) (NP (NN:[53..58] K-ras) (NN:[59..64] point) (NNS:[65..74] mutations))) (PP-LOC (IN:[75..77] in) (NP (NP (NN:[78..84] sputum)) (PP (IN:[85..89] from) (NP (NP (NNS:[90..98] patients)) (PP (IN:[99..103] with) (NP (NP (NN:[104..118] adenocarcinoma)) (PP (IN:[120..122] of) (NP (DT:[123..126] the) (NN:[127..131] lung))))))))) (PP-MNR (IN:[132..134] by) (NP (NN:[135..140] point) (HYPH:[140..141] -) (NN:[141..147] EXACCT))) (.:[147..148] .))) ;section 2 Span:152..206 ;Somers VA, Pietersen AM, Theunissen PH, Thunnissen FB. (SEC (FRAG (NNP:[152..158] Somers) (NNP:[159..161] VA) (,:[161..162] ,) (NNP:[163..172] Pietersen) (VBP:[173..175] AM) (JJ:[175..176] ,) (NNP:[177..187] Theunissen) (NNP:[188..190] PH) (,:[190..191] ,) (NNP:[192..202] Thunnissen) (NNP:[203..206] FB.))) ;section 3 Span:210..290 ;Department of Pathology, Maastricht University, The Netherlands. ;vso@lpat.azm.nl (SEC (FRAG (NNP:[210..220] Department) (IN:[221..223] of) (NNP:[224..233] Pathology) (,:[233..234] ,) (NNP:[235..245] Maastricht) (NNP:[246..256] University) (,:[256..257] ,) (DT:[258..261] The) (NNP:[262..273] Netherlands) (.:[273..274] .) ('':[275..283] vso@lpat) (VBD:[283..287] .azm) (.:[287..290] .nl))) ;sentence 4 Span:294..302 ;PURPOSE: (SENT (NP (NN:[294..301] PURPOSE) (::[301..302] :))) ;sentence 5 Span:303..433 ;Kirsten ras (K-ras) point mutations are found in 30% to 56% of pulmonary ;adenocarcinomas by means of highly sensitive techniques. ;[303..314]:gene-rna:"Kirsten ras" ;[316..321]:gene-rna:"K-ras" ;[323..338]:variation-type:"point mutations" ;[367..392]:malignancy:"pulmonary adenocarcinomas" (SENT (S (NP-SBJ-1 (NML (NML (NNP:[303..310] Kirsten) (NN:[311..314] ras)) (NML (-LRB-:[315..316] -LRB-) (NN:[316..321] K-ras) (-RRB-:[321..322] -RRB-))) (NN:[323..328] point) (NNS:[329..338] mutations)) (VP (VBP:[339..342] are) (VP (VBN:[343..348] found) (NP-1 (-NONE-:[348..348] *)) (PP-LOC (IN:[349..351] in) (NP (NP (CD:[352..354] 30) (NN:[354..355] %)) (PP (TO:[356..358] to) (NP (CD:[359..361] 56) (NN:[361..362] %))) (PP (IN:[363..365] of) (NP (JJ:[367..376] pulmonary) (NNS:[377..392] adenocarcinomas))))) (PP-MNR (IN:[393..395] by) (NP (NP (NNS:[396..401] means)) (PP (IN:[402..404] of) (NP (ADJP (RB:[405..411] highly) (JJ:[412..421] sensitive)) (NNS:[422..432] techniques))))))) (.:[432..433] .))) ;sentence 6 Span:434..634 ;Recently, the Point-EXACCT (point mutation detection using exonuclease ;amplification coupled capture technique) method was described, which ;detected one cell with a mutation in 15,000 normal cells. ;[463..477]:variation-type:"point mutation" ;[494..505]:gene-protein:"exonuclease" ;[601..609]:variation-event:"mutation" (SENT (S (ADVP (RB:[434..442] Recently)) (,:[442..443] ,) (NP-SBJ-2 (NP (DT:[444..447] the) (NML (NML (NN:[449..454] Point) (HYPH:[454..455] -) (NN:[455..461] EXACCT)) (NML (-LRB-:[462..463] -LRB-) (NML (NN:[463..468] point) (NN:[469..477] mutation) (NN:[478..487] detection)) (VP (VBG:[488..493] using) (NP (ADJP (NML (NN:[494..505] exonuclease) (NN:[506..519] amplification)) (VBN:[520..527] coupled)) (NN:[529..536] capture) (NN:[537..546] technique))) (-RRB-:[546..547] -RRB-))) (NN:[548..554] method)) (SBAR-3 (-NONE-:[554..554] *ICH*))) (VP (VBD:[555..558] was) (VP (VBN:[559..568] described) (NP-2 (-NONE-:[568..568] *)) (,:[568..569] ,) (SBAR-3 (WHNP-1 (RB:[570..575] which)) (S (NP-SBJ-1 (-NONE-:[575..575] *T*)) (VP (VBD:[576..584] detected) (NP (NP (CD:[585..588] one) (NN:[589..593] cell)) (PP (IN:[594..598] with) (NP (DT:[599..600] a) (NN:[601..609] mutation)))) (PP-LOC (IN:[611..613] in) (NP (CD:[614..620] 15,000) (JJ:[621..627] normal) (NNS:[628..633] cells)))))))) (.:[633..634] .))) ;sentence 7 Span:635..800 ;The aim of this study was to examine whether K-ras point mutations could be ;found with this rapid method in the sputum of patients with adenocarcinoma ;of the lung. ;[680..685]:gene-rna:"K-ras" ;[686..702]:variation-type:"point mutations" ;[773..799]:malignancy:"adenocarcinoma of the lung" (SENT (S (NP-SBJ (NP (DT:[635..638] The) (NN:[639..642] aim)) (PP (IN:[643..645] of) (NP (DT:[646..650] this) (NN:[651..656] study)))) (VP (VBD:[657..660] was) (S-PRP-PRD (NP-SBJ (-NONE-:[660..660] *)) (VP (TO:[661..663] to) (VP (VB:[664..671] examine) (SBAR (IN:[672..679] whether) (S (NP-SBJ-1 (NN:[680..685] K-ras) (NN:[686..691] point) (NNS:[693..702] mutations)) (VP (MD:[703..708] could) (VP (VB:[709..711] be) (VP (VBN:[712..717] found) (NP-1 (-NONE-:[717..717] *)) (PP-MNR (IN:[718..722] with) (NP (DT:[723..727] this) (JJ:[728..733] rapid) (NN:[734..740] method))) (PP-LOC (IN:[741..743] in) (NP (NP (DT:[744..747] the) (NN:[748..754] sputum)) (PP (IN:[755..757] of) (NP (NP (NNS:[758..766] patients)) (PP (IN:[767..771] with) (NP (NP (NN:[773..787] adenocarcinoma)) (PP (IN:[788..790] of) (NP (DT:[791..794] the) (NN:[795..799] lung)))))))))))))))))) (.:[799..800] .))) ;sentence 8 Span:801..822 ;PATIENTS AND METHODS: (SENT (NP (NNS:[801..809] PATIENTS) (CC:[810..813] AND) (NNS:[814..821] METHODS) (::[821..822] :))) ;sentence 9 Span:823..946 ;DNA from paraffin-embedded adenocarcinoma and corresponding sputum samples ;were analyzed for mutations of the K-ras gene. ;[851..865]:malignancy:"adenocarcinoma" ;[935..940]:gene-rna:"K-ras" (SENT (S (NP-SBJ-1 (NP (NN:[823..826] DNA)) (PP (IN:[827..831] from) (NP (NP (ADJP (NN:[832..840] paraffin) (HYPH:[840..841] -) (VBN:[841..849] embedded)) (NN:[851..865] adenocarcinoma)) (CC:[866..869] and) (NP (JJ:[870..883] corresponding) (NN:[884..890] sputum) (NNS:[891..898] samples))))) (VP (VBD:[899..903] were) (VP (VBN:[904..912] analyzed) (NP-1 (-NONE-:[912..912] *)) (PP-PRP (IN:[913..916] for) (NP (NP (NNS:[917..926] mutations)) (PP (IN:[927..929] of) (NP (DT:[931..934] the) (NN:[935..940] K-ras) (NN:[941..945] gene))))))) (.:[945..946] .))) ;sentence 10 Span:947..1088 ;Twenty-eight biopsy specimens and 54 sputum samples of 22 patients were used ;for amplification and K-ras codon 12 point mutation detection. ;[1047..1052]:gene-rna:"K-ras" ;[1053..1061]:variation-location:"codon 12" ;[1062..1076]:variation-type:"point mutation" (SENT (S (NP-SBJ-1 (NP (CD:[947..959] Twenty-eight) (NN:[960..966] biopsy) (NNS:[967..976] specimens)) (CC:[977..980] and) (NP (NP (CD:[981..983] 54) (NN:[984..990] sputum) (NNS:[991..998] samples)) (PP (IN:[999..1001] of) (NP (CD:[1002..1004] 22) (NNS:[1006..1014] patients))))) (VP (VBD:[1015..1019] were) (VP (VBN:[1020..1024] used) (NP-1 (-NONE-:[1024..1024] *)) (PP-PRP (IN:[1025..1028] for) (NP (NP (NN:[1029..1042] amplification)) (CC:[1043..1046] and) (NP (NML (NML (NN:[1047..1052] K-ras) (NN:[1053..1058] codon) (CD:[1059..1061] 12)) (NN:[1062..1067] point) (NN:[1068..1076] mutation)) (NN:[1078..1087] detection)))))) (.:[1087..1088] .))) ;sentence 11 Span:1089..1097 ;RESULTS: (SENT (NP (NNS:[1089..1096] RESULTS) (::[1096..1097] :))) ;sentence 12 Span:1098..1186 ;In 11 of 22 patients (50%), a mutation in K-ras codon 12 was shown in the ;tumor sample. ;[1140..1145]:gene-rna:"K-ras" ;[1146..1154]:variation-location:"codon 12" ;[1173..1185]:malignancy:"tumor sample" (SENT (S (PP-LOC (IN:[1098..1100] In) (NP (NP (CD:[1101..1103] 11)) (PP (IN:[1104..1106] of) (NP (CD:[1107..1109] 22) (NNS:[1110..1118] patients))) (PRN (-LRB-:[1119..1120] -LRB-) (NP (CD:[1120..1122] 50) (NN:[1122..1123] %)) (-RRB-:[1123..1124] -RRB-)))) (,:[1124..1125] ,) (NP-SBJ-1 (NP (DT:[1126..1127] a) (NN:[1128..1136] mutation)) (PP-LOC (IN:[1137..1139] in) (NP (NN:[1140..1145] K-ras) (NN:[1146..1151] codon) (CD:[1152..1154] 12)))) (VP (VBD:[1155..1158] was) (VP (VBN:[1160..1165] shown) (NP-1 (-NONE-:[1165..1165] *)) (PP-LOC (IN:[1166..1168] in) (NP (DT:[1169..1172] the) (NN:[1173..1178] tumor) (NN:[1179..1185] sample))))) (.:[1185..1186] .))) ;sentence 13 Span:1187..1325 ;In five of 11 patients (45%) with a K-ras mutation in the tumor, the same ;type of mutation was identified in at least one sputum sample. ;[1223..1228]:gene-rna:"K-ras" ;[1246..1251]:malignancy:"tumor" ;[1270..1278]:variation-event:"mutation" (SENT (S (PP-LOC (IN:[1187..1189] In) (NP (NP (CD:[1190..1194] five)) (PP (IN:[1195..1197] of) (NP (NP (CD:[1198..1200] 11) (NNS:[1201..1209] patients)) (PRN (-LRB-:[1210..1211] -LRB-) (CD:[1211..1213] 45) (NN:[1213..1214] %) (-RRB-:[1214..1215] -RRB-)) (PP (IN:[1216..1220] with) (NP (NP (DT:[1221..1222] a) (NN:[1223..1228] K-ras) (NN:[1229..1237] mutation)) (PP (IN:[1238..1240] in) (NP (DT:[1242..1245] the) (NN:[1246..1251] tumor))))))))) (,:[1251..1252] ,) (NP-SBJ-1 (NP (DT:[1253..1256] the) (JJ:[1257..1261] same) (NN:[1262..1266] type)) (PP (IN:[1267..1269] of) (NP (NN:[1270..1278] mutation)))) (VP (VBD:[1279..1282] was) (VP (VBN:[1283..1293] identified) (NP-1 (-NONE-:[1293..1293] *)) (PP-LOC (IN:[1294..1296] in) (NP (QP (IN:[1297..1299] at) (JJS:[1300..1305] least) (CD:[1306..1309] one)) (NN:[1310..1316] sputum) (NN:[1318..1324] sample))))) (.:[1324..1325] .))) ;sentence 14 Span:1326..1431 ;A mutation could not be detected in any of the sputum samples from patients ;with a K-ras-negative tumor. ;[1410..1415]:gene-rna:"K-ras" ;[1425..1430]:malignancy:"tumor" (SENT (S (NP-SBJ-1 (DT:[1326..1327] A) (NN:[1328..1336] mutation)) (VP (MD:[1337..1342] could) (RB:[1343..1346] not) (VP (VB:[1347..1349] be) (VP (VBN:[1350..1358] detected) (NP-1 (-NONE-:[1358..1358] *)) (PP-LOC (IN:[1359..1361] in) (NP (NP (DT:[1362..1365] any)) (PP (IN:[1366..1368] of) (NP (NP (DT:[1369..1372] the) (NN:[1373..1379] sputum) (NNS:[1380..1387] samples)) (PP (IN:[1388..1392] from) (NP (NP (NNS:[1394..1402] patients)) (PP (IN:[1403..1407] with) (NP (DT:[1408..1409] a) (ADJP (NN:[1410..1415] K-ras) (HYPH:[1415..1416] -) (JJ:[1416..1424] negative)) (NN:[1425..1430] tumor)))))))))))) (.:[1430..1431] .))) ;sentence 15 Span:1432..1564 ;Time between K-ras point mutation detection in sputum and clinical diagnosis ;of lung cancer varied from 1 month to almost 4 years. ;[1445..1450]:gene-rna:"K-ras" ;[1451..1465]:variation-type:"point mutation" ;[1513..1524]:malignancy:"lung cancer" (SENT (S (NP-SBJ (NP (NN:[1432..1436] Time)) (PP (IN:[1437..1444] between) (NP (NP (NP (NML (NN:[1445..1450] K-ras) (NN:[1451..1456] point) (NN:[1457..1465] mutation)) (NN:[1467..1476] detection)) (PP-LOC (IN:[1477..1479] in) (NP (NN:[1480..1486] sputum)))) (CC:[1487..1490] and) (NP (NP (JJ:[1491..1499] clinical) (NN:[1500..1509] diagnosis)) (PP (IN:[1510..1512] of) (NP (NN:[1513..1517] lung) (NN:[1518..1524] cancer))))))) (VP (VBD:[1525..1531] varied) (PP-TMP (PP (IN:[1532..1536] from) (NP (CD:[1537..1538] 1) (NN:[1539..1544] month))) (PP (TO:[1545..1547] to) (NP (QP (RB:[1549..1555] almost) (CD:[1556..1557] 4)) (NNS:[1558..1563] years))))) (.:[1563..1564] .))) ;sentence 16 Span:1565..1686 ;In two of the five patients with K-ras-positive sputum specimens, malignant ;cells were found with cytologic examination. ;[1598..1603]:gene-rna:"K-ras" ;[1632..1647]:malignancy:"malignant cells" (SENT (S (PP-LOC (IN:[1565..1567] In) (NP (NP (CD:[1568..1571] two)) (PP (IN:[1572..1574] of) (NP (NP (DT:[1575..1578] the) (CD:[1579..1583] five) (NNS:[1584..1592] patients)) (PP (IN:[1593..1597] with) (NP (ADJP (NN:[1598..1603] K-ras) (HYPH:[1603..1604] -) (JJ:[1604..1612] positive)) (NN:[1613..1619] sputum) (NNS:[1621..1630] specimens))))))) (,:[1630..1631] ,) (NP-SBJ-1 (JJ:[1632..1641] malignant) (NNS:[1642..1647] cells)) (VP (VBD:[1648..1652] were) (VP (VBN:[1653..1658] found) (NP-1 (-NONE-:[1658..1658] *)) (PP-MNR (IN:[1659..1663] with) (NP (JJ:[1664..1673] cytologic) (NN:[1674..1685] examination))))) (.:[1685..1686] .))) ;sentence 17 Span:1687..1698 ;CONCLUSION: (SENT (NP (NN:[1687..1697] CONCLUSION) (::[1697..1698] :))) ;sentence 18 Span:1700..1831 ;Point-EXACCT is suitable for the detection of K-ras point mutations in sputum ; samples of patients with adenocarcinoma of the lung. ;[1746..1751]:gene-rna:"K-ras" ;[1752..1767]:variation-type:"point mutations" ;[1804..1830]:malignancy:"adenocarcinoma of the lung" (SENT (S (NP-SBJ (NN:[1700..1705] Point) (HYPH:[1705..1706] -) (NN:[1706..1712] EXACCT)) (VP (VBZ:[1713..1715] is) (ADJP-PRD (JJ:[1716..1724] suitable) (PP (IN:[1725..1728] for) (NP (NP (DT:[1729..1732] the) (NN:[1733..1742] detection)) (PP (IN:[1743..1745] of) (NP (NN:[1746..1751] K-ras) (NN:[1752..1757] point) (NNS:[1758..1767] mutations))) (PP-LOC (IN:[1768..1770] in) (NP (NP (NN:[1771..1777] sputum) (NNS:[1779..1786] samples)) (PP (IN:[1787..1789] of) (NP (NNS:[1790..1798] patients))) (PP (IN:[1799..1803] with) (NP (NP (NN:[1804..1818] adenocarcinoma)) (PP (IN:[1819..1821] of) (NP (DT:[1822..1825] the) (NN:[1826..1830] lung))))))))))) (.:[1830..1831] .))) ;sentence 19 Span:1832..1925 ;This approach may be an important adjunct to cytology in the early diagnosis ;of lung cancer. ;[1913..1924]:malignancy:"lung cancer" (SENT (S (NP-SBJ (DT:[1832..1836] This) (NN:[1837..1845] approach)) (VP (MD:[1846..1849] may) (VP (VB:[1850..1852] be) (NP-PRD (NP (DT:[1853..1855] an) (JJ:[1857..1866] important) (NN:[1867..1874] adjunct)) (PP (TO:[1875..1877] to) (NP (NN:[1878..1886] cytology)))) (PP (IN:[1887..1889] in) (NP (NP (DT:[1890..1893] the) (JJ:[1894..1899] early) (NN:[1900..1909] diagnosis)) (PP (IN:[1910..1912] of) (NP (NN:[1913..1917] lung) (NN:[1918..1924] cancer))))))) (.:[1924..1925] .))) ;section 20 Span:1929..1973 ;PMID: 9738576 [PubMed - indexed for MEDLINE] (SEC (FRAG (NNP:[1929..1933] PMID) (::[1933..1934] :) (CD:[1935..1942] 9738576) (IN:[1943..1944] -LSB-) (NNP:[1944..1950] PubMed) (HYPH:[1951..1952] -) (JJ:[1953..1960] indexed) (IN:[1961..1964] for) (NNP:[1965..1973] MEDLINE-RSB-)))