;PMID: 8589724 ;source_file_1227.mrg ;Release 0.9 of PennBioIE ;Funded by NSF ITR EIA-0205448 ;0)section:[e:0..31] = [t:0..31] ;1)sentence:[e:36..181] = [t:36..181] ;2)section:[e:185..280] = [t:185..280] ;3)section:[e:284..381] = [t:284..381] ;4)sentence:[e:385..469] = [t:385..469] ;5)sentence:[e:470..657] = [t:470..657] ;6)sentence:[e:658..783] = [t:658..783] ;7)sentence:[e:785..915] = [t:785..915] ;8)sentence:[e:916..1079] = [t:916..1079] ;9)sentence:[e:1080..1258] = [t:1080..1258] ;10)sentence:[e:1259..1460] = [t:1259..1460] ;11)sentence:[e:1461..1585] = [t:1461..1585] ;12)sentence:[e:1586..1679] = [t:1586..1679] ;13)sentence:[e:1680..1762] = [t:1680..1762] ;14)section:[e:1766..1810] = [t:1766..1810] ;section 0 Span:0..31 ;Nat Genet 1996 Mar;12(3):312-4 (SEC (FRAG (VBG:[0..3] Nat) (RB:[4..9] Genet) (CD:[11..15] 1996) (IN:[16..23] Mar;12-LRB-) (CD:[23..24] 3) (-RRB-:[24..25] -RRB-) (CD:[25..29] :312) (::[29..30] -) (CD:[30..31] 4))) ;sentence 1 Span:36..181 ;Somatic c-KIT activating mutation in urticaria pigmentosa and aggressive ;mastocytosis: establishment of clonality in a human mast cell neoplasm. ;[44..49]:gene-rna:"c-KIT" ;[98..122]:malignancy:"aggressive mastocytosis" ;[162..180]:malignancy:"mast cell neoplasm" (SENT (NP-HLN (NP (NP (NP (JJ:[36..43] Somatic) (NN:[44..49] c-KIT) (VBG:[50..60] activating) (NN:[61..69] mutation)) (PP (IN:[70..72] in) (NP (NN:[73..82] urticaria) (NN:[83..93] pigmentosa)))) (CC:[94..97] and) (NP (JJ:[98..108] aggressive) (NN:[110..122] mastocytosis))) (::[122..123] :) (NP (NP (NN:[124..137] establishment)) (PP (IN:[138..140] of) (NP (NN:[141..150] clonality))) (PP (IN:[151..153] in) (NP (DT:[154..155] a) (JJ:[156..161] human) (NML (NN:[162..166] mast) (NN:[167..171] cell)) (NN:[172..180] neoplasm)))) (.:[180..181] .))) ;section 2 Span:185..280 ;Longley BJ, Tyrrell L, Lu SZ, Ma YS, Langley K, Ding TG, Duffy T, Jacobs P, ;Tang LH, Modlin I. (SEC (FRAG (NNP:[185..192] Longley) (NNP:[193..195] BJ) (,:[195..196] ,) (NNP:[197..204] Tyrrell) (NNP:[205..207] L,) (NNP:[208..210] Lu) (NNP:[211..213] SZ) (,:[213..214] ,) (NNP:[215..217] Ma) (NNP:[218..220] YS) (,:[220..221] ,) (NNP:[222..229] Langley) (NNP:[230..231] K) (,:[231..232] ,) (NNP:[233..237] Ding) (NNP:[238..240] TG) (,:[240..241] ,) (NNP:[242..247] Duffy) (NNP:[248..249] T) (,:[249..250] ,) (NNP:[251..257] Jacobs) (NNP:[258..259] P) (,:[259..260] ,) (NNP:[261..265] Tang) (NNP:[267..269] LH) (,:[269..270] ,) (NNP:[271..277] Modlin) (NNP:[278..280] I.))) ;section 3 Span:284..381 ;Department of Dermatology, Yale University School of Medicine, New Haven ;Connecticut 06510, USA. (SEC (FRAG (NNP:[284..294] Department) (IN:[295..297] of) (NNP:[298..309] Dermatology) (IN:[309..310] ,) (NNP:[311..315] Yale) (NNP:[316..326] University) (NNP:[327..333] School) (IN:[334..336] of) (NNP:[337..345] Medicine) (,:[345..346] ,) (NNP:[347..350] New) (NNP:[351..356] Haven) (NNP:[358..369] Connecticut) (NNP:[370..375] 06510) (NNP:[375..376] ,) (NNP:[377..380] USA) (.:[380..381] .))) ;sentence 4 Span:385..469 ;Mastocytosis is characterized by accumulations of mast cells in various ;organs (1). ;[385..397]:malignancy:"Mastocytosis" (SENT (S (NP-SBJ-1 (NN:[385..397] Mastocytosis)) (VP (VBZ:[398..400] is) (VP (VBN:[401..414] characterized) (NP-1 (-NONE-:[414..414] *)) (PP (IN:[415..417] by) (NP-LGS (NP (NNS:[418..431] accumulations)) (PP (IN:[432..434] of) (NP (NN:[435..439] mast) (NNS:[440..445] cells))) (PP (IN:[446..448] in) (NP (JJ:[449..456] various) (NNS:[457..463] organs) (PRN (-LRB-:[465..466] -LRB-) (NP (CD:[466..467] 1)) (-RRB-:[467..468] -RRB-)))))))) (.:[468..469] .))) ;sentence 5 Span:470..657 ;Most cases are indolent and confined to the skin, where discrete mast cell ;infiltrates are associated increased epidermal melanin, a clinical picture ;known as urticaria pigmentosa (UP). ;[593..600]:gene-protein:"melanin" (SENT (S (NP-SBJ-1 (JJS:[470..474] Most) (NNS:[475..480] cases)) (VP (VBP:[481..484] are) (UCP (ADJP-PRD (JJ:[485..493] indolent)) (CC:[494..497] and) (VP (VBN:[498..506] confined) (NP-1 (-NONE-:[506..506] *)) (PP (TO:[507..509] to) (NP (NP (DT:[510..513] the) (NN:[514..518] skin)) (,:[518..519] ,) (SBAR (WHADVP-3 (WRB:[520..525] where)) (S (NP-SBJ-2 (JJ:[526..534] discrete) (NML (NN:[535..539] mast) (NN:[540..544] cell)) (NNS:[546..557] infiltrates)) (VP (VBP:[558..561] are) (VP (VBN:[562..572] associated) (NP-2 (-NONE-:[572..572] *)) (NP (VBN:[573..582] increased) (JJ:[583..592] epidermal) (NN:[593..600] melanin)) (,:[600..601] ,) (NP-ADV (NP (DT:[602..603] a) (JJ:[604..612] clinical) (NN:[613..620] picture)) (VP (VBN:[621..626] known) (NP (-NONE-:[626..626] *)) (PP-CLR (IN:[628..630] as) (NP (NP (NN:[631..640] urticaria) (NN:[641..651] pigmentosa)) (NP (-LRB-:[652..653] -LRB-) (NN:[653..655] UP) (-RRB-:[655..656] -RRB-)))))) (ADVP-LOC-3 (-NONE-:[656..656] *T*))))))))))) (.:[656..657] .))) ;sentence 6 Span:658..783 ;Other forms of mastocytosis combine UP with aggressive involvement of other ;organs or with haemotologic abnormalities (1-4). ;[673..685]:malignancy:"mastocytosis" (SENT (S (NP-SBJ (NP (JJ:[658..663] Other) (NNS:[664..669] forms)) (PP (IN:[670..672] of) (NP (NN:[673..685] mastocytosis)))) (VP (VBP:[686..693] combine) (NP (NP (NN:[694..696] UP)) (PP (PP (IN:[697..701] with) (NP (NP (JJ:[703..713] aggressive) (NN:[714..725] involvement)) (PP (IN:[726..728] of) (NP (JJ:[729..734] other) (NNS:[735..741] organs))))) (CC:[742..744] or) (PP (IN:[745..749] with) (NP (JJ:[750..762] haemotologic) (NNS:[763..776] abnormalities))))) (PRN (-LRB-:[777..778] -LRB-) (NP (CD:[778..779] 1) (HYPH:[779..780] -) (CD:[780..781] 4)) (-RRB-:[781..782] -RRB-))) (.:[782..783] .))) ;sentence 7 Span:785..915 ;It is not known whether all forms of mastocytosis are true neoplasms or ;whether some might represent reactive hyperplasias (5-7). ;[822..834]:malignancy:"mastocytosis" ;[844..853]:malignancy:"neoplasms" ;[887..908]:malignancy:"reactive hyperplasias" (SENT (S (NP-SBJ-1 (NP (PRP:[785..787] It)) (SBAR-2 (-NONE-:[787..787] *EXP*))) (VP (VBZ:[788..790] is) (RB:[791..794] not) (VP (VBN:[795..800] known) (NP-1 (-NONE-:[800..800] *)) (SBAR-2 (SBAR (IN:[801..808] whether) (S (NP-SBJ (NP (DT:[809..812] all) (NNS:[813..818] forms)) (PP (IN:[819..821] of) (NP (NN:[822..834] mastocytosis)))) (VP (VBP:[835..838] are) (NP-PRD (JJ:[839..843] true) (NNS:[844..853] neoplasms))))) (CC:[854..856] or) (SBAR (IN:[857..864] whether) (S (NP-SBJ (DT:[866..870] some)) (VP (MD:[871..876] might) (VP (VB:[877..886] represent) (NP (JJ:[887..895] reactive) (NNS:[896..908] hyperplasias) (PRN (-LRB-:[909..910] -LRB-) (NP (NP (CD:[910..911] 5)) (PP (HYPH:[911..912] -) (NP (CD:[912..913] 7)))) (-RRB-:[913..914] -RRB-)))))))))) (.:[914..915] .))) ;sentence 8 Span:916..1079 ;The c-KIT proto-oncogene encodes a type III receptor tyrosine kinase (KIT) ;that is critical to the development and survival of mast cells and ;melanocytes (8-11). ;[920..925]:gene-rna:"c-KIT" ;[952..985]:gene-protein:"type III receptor tyrosine kinase" ;[987..990]:gene-protein:"KIT" (SENT (S (NP-SBJ (DT:[916..919] The) (NN:[920..925] c-KIT) (AFX:[926..931] proto) (HYPH:[931..932] -) (NN:[932..940] oncogene)) (VP (VBZ:[942..949] encodes) (NP (NP (DT:[950..951] a) (NML (NML (NML (NN:[952..956] type) (CD:[957..960] III)) (NN:[961..969] receptor) (NN:[970..978] tyrosine) (NN:[979..985] kinase)) (NML (-LRB-:[986..987] -LRB-) (NN:[987..990] KIT) (-RRB-:[990..991] -RRB-)))) (SBAR (WHNP-1 (WDT:[992..996] that)) (S (NP-SBJ-1 (-NONE-:[996..996] *T*)) (VP (VBZ:[997..999] is) (ADJP-PRD (JJ:[1000..1008] critical) (PP (TO:[1009..1011] to) (NP (NP (DT:[1012..1015] the) (NN:[1017..1028] development) (CC:[1029..1032] and) (NN:[1033..1041] survival)) (PP (IN:[1042..1044] of) (NP (NP (NN:[1045..1049] mast) (NNS:[1050..1055] cells)) (CC:[1056..1059] and) (NP (NNS:[1060..1071] melanocytes) (PRN (-LRB-:[1072..1073] -LRB-) (NP (NP (CD:[1073..1074] 8)) (PP (HYPH:[1074..1075] -) (NP (CD:[1075..1077] 11)))) (-RRB-:[1077..1078] -RRB-))))))))))))) (.:[1078..1079] .))) ;sentence 9 Span:1080..1258 ;The ligand for KIT (KL) can stimulate mast cell development, proliferation, ;and mediator release (9,12-17), as well as melanocyte proliferation and ;pigment production (18-20). ;[1096..1099]:gene-protein:"KIT" (SENT (S (NP-SBJ (NP (NP (DT:[1080..1083] The) (NN:[1084..1090] ligand)) (PP (IN:[1091..1094] for) (NP (NN:[1096..1099] KIT)))) (NP (-LRB-:[1100..1101] -LRB-) (NN:[1101..1103] KL) (-RRB-:[1103..1104] -RRB-))) (VP (MD:[1105..1108] can) (VP (VB:[1109..1118] stimulate) (NP (NP (NP (NML-1 (NN:[1119..1123] mast) (NN:[1124..1128] cell)) (NN:[1129..1140] development)) (,:[1140..1141] ,) (NP (NML-1 (-NONE-:[1141..1141] *P*)) (NN:[1142..1155] proliferation)) (,:[1155..1156] ,) (CC:[1157..1160] and) (NP (NML-1 (-NONE-:[1160..1160] *P*)) (NN:[1161..1169] mediator) (NN:[1171..1178] release)) (PRN (-LRB-:[1179..1180] -LRB-) (NP (NP (CD:[1180..1181] 9)) (,:[1181..1182] ,) (NP (NP (CD:[1182..1184] 12)) (PP (HYPH:[1184..1185] -) (NP (CD:[1185..1187] 17))))) (-RRB-:[1187..1188] -RRB-))) (,:[1188..1189] ,) (CONJP (RB:[1190..1192] as) (RB:[1193..1197] well) (IN:[1198..1200] as)) (NP (NP (NN:[1201..1211] melanocyte) (NN:[1212..1225] proliferation)) (CC:[1226..1229] and) (NP (NN:[1230..1237] pigment) (NN:[1238..1248] production) (PRN (-LRB-:[1250..1251] -LRB-) (NP (NP (CD:[1251..1253] 18)) (PP (HYPH:[1253..1254] -) (NP (CD:[1254..1256] 20)))) (-RRB-:[1256..1257] -RRB-))))))) (.:[1257..1258] .))) ;sentence 10 Span:1259..1460 ;To determine the role of c-KIT in the pathogenesis of mastocytosis, we ;examined tissue and cells isolated from a patient with UP and aggressive ;systemic mastocytosis with massive splenic involvement. ;[1284..1289]:gene-rna:"c-KIT" ;[1313..1325]:malignancy:"mastocytosis" ;[1393..1426]:malignancy:"aggressive systemic mastocytosis" (SENT (S (S-PRP (NP-SBJ (-NONE-:[1259..1259] *)) (VP (TO:[1259..1261] To) (VP (VB:[1262..1271] determine) (NP (NP (DT:[1272..1275] the) (NN:[1276..1280] role)) (PP (IN:[1281..1283] of) (NP (NN:[1284..1289] c-KIT))) (PP (IN:[1290..1292] in) (NP (NP (DT:[1293..1296] the) (NN:[1297..1309] pathogenesis)) (PP (IN:[1310..1312] of) (NP (NN:[1313..1325] mastocytosis))))))))) (,:[1325..1326] ,) (NP-SBJ (PRP:[1327..1329] we)) (VP (VBD:[1331..1339] examined) (NP (NP (NN:[1340..1346] tissue) (CC:[1347..1350] and) (NNS:[1351..1356] cells)) (VP (VBN:[1357..1365] isolated) (NP (-NONE-:[1365..1365] *)) (PP-CLR (IN:[1366..1370] from) (NP (NP (DT:[1371..1372] a) (NN:[1373..1380] patient)) (PP (IN:[1381..1385] with) (NP (NP (NN:[1386..1388] UP)) (CC:[1389..1392] and) (NP (NP (JJ:[1393..1403] aggressive) (JJ:[1405..1413] systemic) (NN:[1414..1426] mastocytosis)) (PP (IN:[1427..1431] with) (NP (JJ:[1432..1439] massive) (JJ:[1440..1447] splenic) (NN:[1448..1459] involvement))))))))))) (.:[1459..1460] .))) ;sentence 11 Span:1461..1585 ;We found a mutation that results in constitutive activation and expression ;of c-KIT in mast cells of both skin and spleen. ;[1540..1545]:gene-rna:"c-KIT" (SENT (S (NP-SBJ (PRP:[1461..1463] We)) (VP (VBD:[1464..1469] found) (NP (NP (DT:[1470..1471] a) (NN:[1472..1480] mutation)) (SBAR (WHNP-1 (WDT:[1481..1485] that)) (S (NP-SBJ-1 (-NONE-:[1485..1485] *T*)) (VP (VBZ:[1487..1494] results) (PP-CLR (IN:[1495..1497] in) (NP (NP (NP (JJ:[1498..1510] constitutive) (NN:[1511..1521] activation)) (CC:[1522..1525] and) (NP (NN:[1526..1536] expression))) (PP (IN:[1537..1539] of) (NP (NN:[1540..1545] c-KIT))))) (PP (IN:[1546..1548] in) (NP (NP (NN:[1549..1553] mast) (NNS:[1554..1559] cells)) (PP (IN:[1560..1562] of) (NP (CC:[1563..1567] both) (NN:[1569..1573] skin) (CC:[1574..1577] and) (NN:[1578..1584] spleen)))))))))) (.:[1584..1585] .))) ;sentence 12 Span:1586..1679 ;This is the first in situ demonstration of an activation c-KIT mutation in ;neoplastic cells. ;[1643..1648]:gene-rna:"c-KIT" (SENT (S (NP-SBJ (DT:[1586..1590] This)) (VP (VBZ:[1591..1593] is) (NP-PRD (NP (DT:[1594..1597] the) (JJ:[1598..1603] first) (ADJP (FW:[1604..1606] in) (FW:[1607..1611] situ)) (NN:[1612..1625] demonstration)) (PP (IN:[1626..1628] of) (NP (NP (DT:[1629..1631] an) (NN:[1632..1642] activation) (NN:[1643..1648] c-KIT) (NN:[1650..1658] mutation)) (PP (IN:[1659..1661] in) (NP (JJ:[1662..1672] neoplastic) (NNS:[1673..1678] cells))))))) (.:[1678..1679] .))) ;sentence 13 Span:1680..1762 ;It also demonstrates the clonal and neoplastic nature of this form of ;mastocytes. (SENT (S (NP-SBJ (PRP:[1680..1682] It)) (ADVP (RB:[1683..1687] also)) (VP (VBZ:[1688..1700] demonstrates) (NP (NP (DT:[1701..1704] the) (ADJP (JJ:[1705..1711] clonal) (CC:[1712..1715] and) (JJ:[1716..1726] neoplastic)) (NN:[1728..1734] nature)) (PP (IN:[1735..1737] of) (NP (NP (DT:[1738..1742] this) (NN:[1743..1747] form)) (PP (IN:[1748..1750] of) (NP (NNS:[1751..1761] mastocytes))))))) (.:[1761..1762] .))) ;section 14 Span:1766..1810 ;PMID: 8589724 [PubMed - indexed for MEDLINE] (SEC (FRAG (NNP:[1766..1770] PMID) (::[1770..1771] :) (CD:[1772..1779] 8589724) (NN:[1780..1781] -LSB-) (NNP:[1781..1787] PubMed) (::[1788..1789] -) (NN:[1790..1797] indexed) (IN:[1798..1801] for) (NNP:[1802..1810] MEDLINE-RSB-)))