;PMID: 9856847 ;source_file_1379.mrg ;Release 0.9 of PennBioIE ;Funded by NSF ITR EIA-0205448 ;0)section:[e:0..42] = [t:0..42] ;1)sentence:[e:47..210] = [t:47..210] ;2)section:[e:214..262] = [t:214..262] ;3)section:[e:266..339] = [t:266..339] ;4)sentence:[e:343..715] = [t:343..715] ;5)sentence:[e:716..816] = [t:716..816] ;6)sentence:[e:817..1065] = [t:817..1065] ;7)sentence:[e:1066..1239] = [t:1066..1239] ;8)sentence:[e:1240..1426] = [t:1240..1426] ;9)sentence:[e:1427..1551] = [t:1427..1551] ;10)sentence:[e:1552..1745] = [t:1552..1745] ;11)sentence:[e:1746..2086] = [t:1746..2086] ;12)section:[e:2090..2134] = [t:2090..2134] ;section 0 Span:0..42 ;J Invest Dermatol 1998 Dec;111(6):1227-31 (SEC (FRAG (NNP:[0..1] J) (DT:[2..8] Invest) (NNP:[9..17] Dermatol) (CD:[19..23] 1998) (.:[24..32] Dec;111-LRB-) (CD:[32..34] 6-RRB-) (CD:[34..39] :1227) (HYPH:[39..40] -) (CD:[40..42] 31))) ;sentence 1 Span:47..210 ;Identification of activating c-kit mutations in adult-, but not in ;childhood-onset indolent mastocytosis: a possible explanation for divergent ;clinical behavior. ;[76..81]:gene-rna:"c-kit" ;[95..101]...[125..152]:malignancy:"adult-"..."onset indolent mastocytosis" ;[115..152]:malignancy:"childhood-onset indolent mastocytosis" (SENT (NP-HLN (NP (NP (NN:[47..61] Identification)) (PP (IN:[62..64] of) (NP (VBG:[65..75] activating) (NN:[76..81] c-kit) (NNS:[82..91] mutations))) (PP (PP (IN:[92..94] in) (NP (NML (NN:[95..100] adult) (HYPH:[100..101] -) (NML-1 (-NONE-:[101..101] *RNR*))) (NML-2 (-NONE-:[101..101] *RNR*)))) (,:[101..102] ,) (CONJP (CC:[103..106] but) (RB:[107..110] not)) (PP (IN:[111..113] in) (NP (NML (NN:[115..124] childhood) (HYPH:[124..125] -) (NML-1 (-NONE-:[125..125] *RNR*))) (NML-2 (-NONE-:[125..125] *RNR*)))) (NML-1 (NN:[125..130] onset)) (NML-2 (JJ:[131..139] indolent) (NN:[140..152] mastocytosis)))) (::[152..153] :) (NP (NP (DT:[154..155] a) (JJ:[156..164] possible) (NN:[165..176] explanation)) (PP (IN:[177..180] for) (NP (JJ:[181..190] divergent) (JJ:[192..200] clinical) (NN:[201..209] behavior)))) (.:[209..210] .))) ;section 2 Span:214..262 ;Buttner C, Henz BM, Welker P, Sepp NT, Grabbe J. (SEC (FRAG (NNP:[214..221] Buttner) (NNP:[222..223] C) (,:[223..224] ,) (NNP:[225..229] Henz) (NNP:[230..232] BM) (,:[232..233] ,) (NNP:[234..240] Welker) (NNP:[241..242] P) (,:[242..243] ,) (NNP:[244..248] Sepp) (NNP:[249..251] NT) (,:[251..252] ,) (NNP:[253..259] Grabbe) (NNP:[260..262] J.))) ;section 3 Span:266..339 ;Department of Dermatology, Charite, Humboldt University, Berlin, Germany. (SEC (FRAG (NNP:[266..276] Department) (IN:[277..279] of) (NNP:[280..291] Dermatology) (,:[291..292] ,) (NNP:[293..300] Charite) (,:[300..301] ,) (NNP:[302..310] Humboldt) (NNP:[311..321] University) (,:[321..322] ,) (NNP:[323..329] Berlin) (,:[329..330] ,) (NNP:[331..338] Germany) (.:[338..339] .))) ;sentence 4 Span:343..715 ;Mastocytosis represents a mast cell proliferative disease that generally runs ;a benign clinical course, with spontaneous remissions mostly by puberty in ;childhood-onset disease, although rare forms, particularly in adult-onset ;disease, can be associated with (pre)malignant hematologic disorders and very ; rarely present as mast cell leukemia or malignant mastocytosis. ;[343..355]:malignancy:"Mastocytosis" ;[498..521]:malignancy:"childhood-onset disease" ;[560..580]:malignancy:"adult-onset disease" ;[670..688]:malignancy:"mast cell leukemia" ;[692..714]:malignancy:"malignant mastocytosis" (SENT (S (NP-SBJ (NN:[343..355] Mastocytosis)) (VP (VBZ:[356..366] represents) (NP (NP (DT:[367..368] a) (NML (NN:[369..373] mast) (NN:[374..378] cell)) (JJ:[379..392] proliferative) (NN:[393..400] disease)) (SBAR (WHNP-2 (WDT:[401..405] that)) (S (NP-SBJ-2 (-NONE-:[405..405] *T*)) (ADVP (RB:[406..415] generally)) (VP (VBZ:[416..420] runs) (NP (DT:[421..422] a) (JJ:[424..430] benign) (JJ:[431..439] clinical) (NN:[440..446] course))))) (,:[446..447] ,) (PP (IN:[448..452] with) (NP (NP (JJ:[453..464] spontaneous) (NNS:[465..475] remissions)) (PP (ADVP (RB:[476..482] mostly)) (IN:[483..485] by) (NP (NN:[486..493] puberty))) (PP (IN:[494..496] in) (NP (NML (NN:[498..507] childhood) (HYPH:[507..508] -) (NN:[508..513] onset)) (NN:[514..521] disease)))))) (,:[521..522] ,) (SBAR-ADV (IN:[523..531] although) (S (NP-SBJ-1 (JJ:[532..536] rare) (NNS:[537..542] forms)) (,:[542..543] ,) (PP (ADVP (RB:[544..556] particularly)) (IN:[557..559] in) (NP (NML (NN:[560..565] adult) (HYPH:[565..566] -) (NN:[566..571] onset)) (NN:[573..580] disease))) (,:[580..581] ,) (VP (VP (MD:[582..585] can) (VP (VB:[586..588] be) (VP (VBN:[589..599] associated) (NP-1 (-NONE-:[599..599] *)) (PP-CLR (IN:[600..604] with) (NP (JJ:[605..619] -LRB-pre-RRB-malignant) (JJ:[620..631] hematologic) (NNS:[632..641] disorders)))))) (CC:[642..645] and) (VP (ADVP (RB:[646..650] very) (RB:[652..658] rarely)) (VBP:[659..666] present) (PP (IN:[667..669] as) (NP (NP (NML (NN:[670..674] mast) (NN:[675..679] cell)) (NN:[680..688] leukemia)) (CC:[689..691] or) (NP (JJ:[692..701] malignant) (NN:[702..714] mastocytosis))))))))) (.:[714..715] .))) ;sentence 5 Span:716..816 ;Reasons for this divergent clinical behavior of childhood- versus ;adult-onset disease are unknown. ;[765..775]...[789..802]:malignancy:"childhood-"..."onset disease" ;[783..802]:malignancy:"adult-onset disease" (SENT (S (NP-SBJ (NP (NNS:[716..723] Reasons)) (PP (IN:[724..727] for) (NP (NP (DT:[728..732] this) (JJ:[734..743] divergent) (JJ:[744..752] clinical) (NN:[753..761] behavior)) (PP (IN:[762..764] of) (NP (NP (NML (NN:[765..774] childhood) (HYPH:[774..775] -) (NML-1 (-NONE-:[775..775] *RNR*))) (NML-2 (-NONE-:[775..775] *RNR*))) (PP (IN:[776..782] versus) (NP (NML (NN:[783..788] adult) (HYPH:[788..789] -) (NML-1 (-NONE-:[789..789] *RNR*))) (NML-2 (-NONE-:[789..789] *RNR*)))) (NML-1 (NN:[789..794] onset)) (NML-2 (NN:[795..802] disease))))))) (VP (VBP:[803..806] are) (ADJP-PRD (JJ:[808..815] unknown))) (.:[815..816] .))) ;sentence 6 Span:817..1065 ;Recently, two activating mutations in the intracellular domain of the ;proto-oncogene c-kit, which encodes a tyrosine kinase receptor for the mast ;cell growth factor stem cell factor, have been detected in the human ;leukemic mast cell line HMC-1. ;[903..908]:gene-rna:"c-kit" ;[926..950]:gene-protein:"tyrosine kinase receptor" ;[959..1000]:gene-protein:"mast cell growth factor stem cell factor" ;[1034..1053]:malignancy:"leukemic mast cell" (SENT (S (ADVP-TMP (RB:[817..825] Recently)) (,:[825..826] ,) (NP-SBJ-2 (NP (CD:[827..830] two) (VBG:[831..841] activating) (NNS:[842..851] mutations)) (PP (IN:[852..854] in) (NP (NP (DT:[855..858] the) (JJ:[859..872] intracellular) (NN:[873..879] domain)) (PP (IN:[880..882] of) (NP (NP (NP (DT:[883..886] the) (AFX:[888..893] proto) (HYPH:[893..894] -) (NN:[894..902] oncogene)) (NP (NN:[903..908] c-kit))) (,:[908..909] ,) (SBAR (WHNP-1 (WDT:[910..915] which)) (S (NP-SBJ-1 (-NONE-:[915..915] *T*)) (VP (VBZ:[916..923] encodes) (NP (NP (DT:[924..925] a) (NN:[926..934] tyrosine) (NN:[935..941] kinase) (NN:[942..950] receptor)) (PP (IN:[951..954] for) (NP (DT:[955..958] the) (NML (NML (NN:[959..963] mast) (NN:[964..968] cell)) (NML (NN:[970..976] growth) (NN:[977..983] factor))) (NML (NML (NN:[984..988] stem) (NN:[989..993] cell)) (NN:[994..1000] factor))))))))))))) (,:[1000..1001] ,) (VP (VBP:[1002..1006] have) (VP (VBN:[1007..1011] been) (VP (VBN:[1012..1020] detected) (NP-2 (-NONE-:[1020..1020] *)) (PP (IN:[1021..1023] in) (NP (NML (DT:[1024..1027] the) (JJ:[1028..1033] human) (JJ:[1034..1042] leukemic) (NML (NN:[1043..1047] mast) (NN:[1049..1053] cell)) (NN:[1054..1058] line)) (NML (NN:[1059..1064] HMC-1))))))) (.:[1064..1065] .))) ;sentence 7 Span:1066..1239 ;We have therefore studied lesional skin biopsies from patients with adult- ;and childhood-onset indolent mastocytosis for the presence of these codon ;560 and 816 mutations. ;[1135..1141]...[1156..1183]:malignancy:"adult-"..."onset indolent ;mastocytosis" ;[1146..1183]:malignancy:"childhood-onset indolent mastocytosis" ;[1211..1220]:variation-location:"codon 560" ;[1211..1216]...[1225..1228]:variation-location:"codon"..."816" ;[1229..1238]:variation-event:"mutations" (SENT (S (NP-SBJ (PRP:[1066..1068] We)) (VP (VBP:[1069..1073] have) (ADVP (RB:[1074..1083] therefore)) (VP (VBN:[1084..1091] studied) (NP (NP (JJ:[1092..1100] lesional) (NN:[1101..1105] skin) (NNS:[1106..1114] biopsies)) (PP (IN:[1115..1119] from) (NP (NP (NNS:[1120..1128] patients)) (PP (IN:[1130..1134] with) (NP (NP (NML (NN:[1135..1140] adult) (HYPH:[1140..1141] -) (NML-3 (-NONE-:[1141..1141] *P*))) (NML-4 (-NONE-:[1141..1141] *P*))) (CC:[1142..1145] and) (NP (NML (NN:[1146..1155] childhood) (HYPH:[1155..1156] -) (NML-3 (NN:[1156..1161] onset))) (NML-4 (JJ:[1162..1170] indolent) (NN:[1171..1183] mastocytosis)))))))) (PP (IN:[1184..1187] for) (NP (NP (DT:[1188..1191] the) (NN:[1192..1200] presence)) (PP (IN:[1201..1203] of) (NP (DT:[1204..1209] these) (NML (NML (NML (NML-2 (NN:[1211..1216] codon)) (CD:[1217..1220] 560)) (NML-1 (-NONE-:[1220..1220] *P*))) (CC:[1221..1224] and) (NML (NML (NML-2 (-NONE-:[1224..1224] *P*)) (CD:[1225..1228] 816)) (NML-1 (NNS:[1229..1238] mutations)))))))))) (.:[1238..1239] .))) ;sentence 8 Span:1240..1426 ;C-kit coding DNA sequences were amplified and analyzed by mutation-specific ;restriction analyses, and mutated polymerase chain reaction products were ;additionally cloned and sequenced. ;[1240..1245]:gene-rna:"C-kit" ;[1351..1361]:gene-protein:"polymerase" (SENT (S (S (NP-SBJ-2 (NN:[1240..1245] C-kit) (VBG:[1246..1252] coding) (NN:[1253..1256] DNA) (NNS:[1257..1266] sequences)) (VP (VBD:[1267..1271] were) (VP (VBN:[1272..1281] amplified) (CC:[1282..1285] and) (VBN:[1287..1295] analyzed) (NP-2 (-NONE-:[1295..1295] *)) (PP-MNR (IN:[1296..1298] by) (NP (NML (NN:[1299..1307] mutation) (HYPH:[1307..1308] -) (JJ:[1308..1316] specific)) (NN:[1317..1328] restriction) (NNS:[1329..1337] analyses)))))) (,:[1337..1338] ,) (CC:[1339..1342] and) (S (NP-SBJ-1 (VBN:[1343..1350] mutated) (NML (NN:[1351..1361] polymerase) (NN:[1362..1367] chain) (NN:[1369..1377] reaction)) (NNS:[1378..1386] products)) (VP (VBD:[1387..1391] were) (ADVP (RB:[1392..1404] additionally)) (VP (VBN:[1405..1411] cloned) (CC:[1412..1415] and) (VBN:[1416..1425] sequenced) (NP-1 (-NONE-:[1425..1425] *))))) (.:[1425..1426] .))) ;sentence 9 Span:1427..1551 ;The codon 816 mutation was found in all six samples from adult patients, but ;not in any of the 11 specimens from children. ;[1431..1440]:variation-location:"codon 816" ;[1441..1449]:variation-event:"mutation" (SENT (S (NP-SBJ-2 (DT:[1427..1430] The) (NML (NN:[1431..1436] codon) (CD:[1437..1440] 816)) (NN:[1441..1449] mutation)) (VP (VBD:[1451..1454] was) (VP (VP (VBN:[1455..1460] found) (NP-2 (-NONE-:[1460..1460] *)) (PP=1 (IN:[1461..1463] in) (NP (NP (DT:[1464..1467] all) (CD:[1468..1471] six) (NNS:[1472..1479] samples)) (PP (IN:[1480..1484] from) (NP (JJ:[1485..1490] adult) (NNS:[1491..1499] patients)))))) (,:[1499..1500] ,) (CC:[1501..1504] but) (VP (RB:[1505..1508] not) (PP=1 (IN:[1509..1511] in) (NP (NP (DT:[1512..1515] any)) (PP (IN:[1516..1518] of) (NP (NP (DT:[1519..1522] the) (CD:[1523..1525] 11) (NNS:[1527..1536] specimens)) (PP (IN:[1537..1541] from) (NP (NNS:[1542..1550] children)))))))))) (.:[1550..1551] .))) ;sentence 10 Span:1552..1745 ;In addition, the codon 560 mutation could be demonstrated for the first time ;in indolent mastocytosis, namely in two of four specimens from adult ;patients, but not in those from two children. ;[1569..1578]:variation-location:"codon 560" ;[1579..1587]:variation-event:"mutation" ;[1633..1654]:malignancy:"indolent mastocytosis" (SENT (S (PP (IN:[1552..1554] In) (NP (NN:[1555..1563] addition))) (,:[1563..1564] ,) (NP-SBJ-1 (DT:[1565..1568] the) (NML (NN:[1569..1574] codon) (CD:[1575..1578] 560)) (NN:[1579..1587] mutation)) (VP (MD:[1588..1593] could) (VP (VB:[1594..1596] be) (VP (VBN:[1598..1610] demonstrated) (NP-1 (-NONE-:[1610..1610] *)) (PP (IN:[1611..1614] for) (NP (DT:[1615..1618] the) (JJ:[1619..1624] first) (NN:[1625..1629] time))) (PP (IN:[1630..1632] in) (NP (JJ:[1633..1641] indolent) (NN:[1642..1654] mastocytosis))) (,:[1654..1655] ,) (PP (PP (ADVP (RB:[1656..1662] namely)) (IN:[1663..1665] in) (NP (NP (CD:[1666..1669] two)) (PP (IN:[1670..1672] of) (NP (NP (CD:[1673..1677] four) (NNS:[1679..1688] specimens)) (PP (IN:[1689..1693] from) (NP (JJ:[1694..1699] adult) (NNS:[1700..1708] patients))))))) (,:[1708..1709] ,) (CONJP (CC:[1710..1713] but) (RB:[1714..1717] not)) (PP (IN:[1718..1720] in) (NP (NP (DT:[1721..1726] those)) (PP (IN:[1727..1731] from) (NP (CD:[1732..1735] two) (NNS:[1736..1744] children))))))))) (.:[1744..1745] .))) ;sentence 11 Span:1746..2086 ;These data thus provide a possible explanation for the divergent clinical ;behavior of adult- versus childhood-onset indolent mastocytosis, with the ;first being associated with an activating mutation, possibly as part of a ;neoplastic process, and the latter representing most likely a reactive ;process of an as yet unknown pathogenesis. ;[1834..1840]...[1858..1885]:malignancy:"adult-"..."onset indolent ;mastocytosis" ;[1848..1885]:malignancy:"childhood-onset indolent mastocytosis" (SENT (S (NP-SBJ (DT:[1746..1751] These) (NNS:[1752..1756] data)) (ADVP (RB:[1758..1762] thus)) (VP (VBP:[1763..1770] provide) (NP (NP (DT:[1771..1772] a) (JJ:[1773..1781] possible) (NN:[1782..1793] explanation)) (PP (IN:[1794..1797] for) (NP (NP (DT:[1798..1801] the) (JJ:[1802..1811] divergent) (JJ:[1812..1820] clinical) (NN:[1821..1829] behavior)) (PP (IN:[1830..1832] of) (NP (NP (NML (NN:[1834..1839] adult) (HYPH:[1839..1840] -) (NML-2 (-NONE-:[1840..1840] *RNR*))) (NML-3 (-NONE-:[1840..1840] *RNR*))) (PP (IN:[1841..1847] versus) (NP (NML (NN:[1848..1857] childhood) (HYPH:[1857..1858] -) (NML-2 (-NONE-:[1858..1858] *RNR*))) (NML-3 (-NONE-:[1858..1858] *RNR*)))) (NML-2 (NN:[1858..1863] onset)) (NML-3 (JJ:[1864..1872] indolent) (NN:[1873..1885] mastocytosis))))))) (,:[1885..1886] ,) (PP (IN:[1887..1891] with) (S-NOM (S (NP-SBJ-1 (DT:[1892..1895] the) (JJ:[1896..1901] first)) (VP (VBG:[1902..1907] being) (VP (VBN:[1909..1919] associated) (NP-1 (-NONE-:[1919..1919] *)) (PP-CLR (IN:[1920..1924] with) (NP (DT:[1925..1927] an) (VBG:[1928..1938] activating) (NN:[1939..1947] mutation))) (,:[1947..1948] ,) (PP (ADVP (RB:[1949..1957] possibly)) (IN:[1958..1960] as) (NP (NP (NN:[1961..1965] part)) (PP (IN:[1966..1968] of) (NP (DT:[1969..1970] a) (JJ:[1971..1981] neoplastic) (NN:[1983..1990] process)))))))) (,:[1990..1991] ,) (CC:[1992..1995] and) (S (NP-SBJ (DT:[1996..1999] the) (JJ:[2000..2006] latter)) (VP (VBG:[2007..2019] representing) (ADVP (RBS:[2020..2024] most) (RB:[2025..2031] likely)) (NP (NP (DT:[2032..2033] a) (JJ:[2034..2042] reactive) (NN:[2043..2050] process)) (PP (IN:[2051..2053] of) (NP (DT:[2054..2056] an) (ADJP (ADVP (RB:[2057..2059] as) (RB:[2060..2063] yet)) (JJ:[2065..2072] unknown)) (NN:[2073..2085] pathogenesis))))))))) (.:[2085..2086] .))) ;section 12 Span:2090..2134 ;PMID: 9856847 [PubMed - indexed for MEDLINE] (SEC (FRAG (NNP:[2090..2094] PMID) (::[2094..2095] :) (CD:[2096..2103] 9856847) (IN:[2104..2105] -LSB-) (NNP:[2105..2111] PubMed) (HYPH:[2112..2113] -) (JJ:[2114..2121] indexed) (IN:[2122..2125] for) (NNP:[2126..2134] MEDLINE-RSB-)))