;PMID: 8852654 ;source_file_2853.mrg ;Release 0.9 of PennBioIE ;Funded by NSF ITR EIA-0205448 ;0)section:[e:0..37] = [t:0..37] ;1)sentence:[e:43..143] = [t:43..143] ;2)section:[e:147..215] = [t:147..215] ;3)section:[e:219..273] = [t:219..273] ;4)sentence:[e:277..394] = [t:277..394] ;5)sentence:[e:395..494] = [t:395..494] ;6)sentence:[e:495..619] = [t:495..619] ;7)sentence:[e:620..797] = [t:620..797] ;8)sentence:[e:798..977] = [t:798..977] ;9)sentence:[e:978..1038] = [t:978..1038] ;10)sentence:[e:1039..1172] = [t:1039..1172] ;11)sentence:[e:1173..1306] = [t:1173..1306] ;12)section:[e:1310..1354] = [t:1310..1354] ;section 0 Span:0..37 ;Hum Mol Genet. 1996 Mar;5(3):309-17. (SEC (FRAG (NNP:[0..3] Hum) (NNP:[4..7] Mol) (NNP:[8..13] Genet) (.:[13..14] .) (CD:[16..20] 1996) (IN:[21..25] Mar;) (CD:[25..26] 5) (NN:[26..27] -LRB-) (NN:[27..28] 3) (-RRB-:[28..29] -RRB-) (::[29..30] :) (CD:[30..33] 309) (CD:[33..36] -17) (.:[36..37] .))) ;sentence 1 Span:43..143 ;A human modifier of methylation for class I HLA genes (MEMO-1) maps to ;chromosomal bands 1p35-36.1. ;[79..90]:gene-rna:"class I HLA" ;[98..104]:gene-rna:"MEMO-1" ;[133..142]:variation-location:"1p35-36.1" (SENT (S-HLN (NP-SBJ (NP (DT:[43..44] A) (JJ:[45..50] human) (NN:[51..59] modifier)) (PP (IN:[60..62] of) (NP (NP (NN:[63..74] methylation)) (PP (IN:[75..78] for) (NP (NML (NN:[79..84] class) (CD:[85..86] I)) (NN:[87..90] HLA) (NNS:[91..96] genes) (PRN (-LRB-:[97..98] -LRB-) (NP (NN:[98..104] MEMO-1)) (-RRB-:[104..105] -RRB-))))))) (VP (VBZ:[106..110] maps) (PP (TO:[111..113] to) (NP (NP (JJ:[115..126] chromosomal) (NNS:[127..132] bands)) (NP (NN:[133..135] 1p) (CD:[135..137] 35) (HYPH:[137..138] -) (CD:[138..142] 36.1))))) (.:[142..143] .))) ;section 2 Span:147..215 ;Cheng NC, Chan AJ, Beitsma MM, Speleman F, Westerveld A, Versteeg R. (SEC (FRAG (NNP:[147..152] Cheng) (NNP:[153..155] NC) (,:[155..156] ,) (NNP:[157..161] Chan) (NNP:[162..164] AJ) (,:[164..165] ,) (NNP:[166..173] Beitsma) (NNP:[174..176] MM) (,:[176..177] ,) (NNP:[178..186] Speleman) (NNP:[187..188] F) (,:[188..189] ,) (NNP:[190..200] Westerveld) (NNP:[201..202] A) (,:[202..203] ,) (NNP:[204..212] Versteeg) (NNP:[213..215] R.))) ;section 3 Span:219..273 ;Department of Human Genetics, University of Amsterdam. (SEC (FRAG (NNP:[219..229] Department) (IN:[230..232] of) (NNP:[233..238] Human) (NNP:[239..247] Genetics) (,:[247..248] ,) (NNP:[249..259] University) (IN:[260..262] of) (NNP:[263..272] Amsterdam) (.:[272..273] .))) ;sentence 4 Span:277..394 ;Class I HLA genes are expressed in almost all tissues, but expression is low ;or undetectable in many neuroblastomas. ;[277..288]:gene-rna:"Class I HLA" ;[379..393]:malignancy-type:"neuroblastomas" (SENT (S (S (NP-SBJ-1 (NML (NML (NN:[277..282] Class) (CD:[283..284] I)) (NN:[285..288] HLA)) (NNS:[289..294] genes)) (VP (VBP:[295..298] are) (VP (VBN:[299..308] expressed) (NP-1 (-NONE-:[308..308] *)) (PP (IN:[309..311] in) (NP (RB:[312..318] almost) (DT:[319..322] all) (NNS:[323..330] tissues)))))) (,:[330..331] ,) (CC:[332..335] but) (S (NP-SBJ (NN:[336..346] expression)) (VP (VBZ:[347..349] is) (ADJP-PRD (JJ:[350..353] low) (CC:[354..356] or) (JJ:[358..370] undetectable)) (PP-LOC (IN:[371..373] in) (NP (JJ:[374..378] many) (NNS:[379..393] neuroblastomas))))) (.:[393..394] .))) ;sentence 5 Span:395..494 ;We analysed class I HLA methylation in normal tissues and in 28 ;neuroectodermal tumour cell lines. ;[407..418]:gene-rna:"class I HLA" ;[460..482]:malignancy-type:"neuroectodermal tumour" (SENT (S (NP-SBJ (PRP:[395..397] We)) (VP (VBD:[398..406] analysed) (NP (NML (NN:[407..412] class) (CD:[413..414] I)) (NN:[415..418] HLA) (NN:[419..430] methylation)) (PP-LOC (PP (IN:[431..433] in) (NP (JJ:[435..441] normal) (NNS:[442..449] tissues))) (CC:[450..453] and) (PP (IN:[454..456] in) (NP (CD:[457..459] 28) (JJ:[460..475] neuroectodermal) (NN:[476..482] tumour) (NN:[483..487] cell) (NNS:[488..493] lines))))) (.:[493..494] .))) ;sentence 6 Span:495..619 ;HLA-C is hypermethylated in normal adult tissues and 13 cell lines, while 15 ;cell lines show the hypomethylated phenotype. ;[495..500]:gene-rna:"HLA-C" (SENT (S (NP-SBJ-1 (NN:[495..500] HLA-C)) (VP (VBZ:[501..503] is) (VP (VBN:[505..520] hypermethylated) (NP-1 (-NONE-:[520..520] *)) (PP (IN:[521..523] in) (NP (NP (JJ:[524..530] normal) (JJ:[531..536] adult) (NNS:[537..544] tissues)) (CC:[545..548] and) (NP (CD:[549..551] 13) (NN:[552..556] cell) (NNS:[557..562] lines)))) (,:[562..563] ,) (SBAR-ADV (IN:[564..569] while) (S (NP-SBJ (CD:[570..572] 15) (NN:[573..577] cell) (NNS:[578..583] lines)) (VP (VBP:[585..589] show) (NP (DT:[590..593] the) (VBN:[594..608] hypomethylated) (NN:[609..618] phenotype))))))) (.:[618..619] .))) ;sentence 7 Span:620..797 ;Hypomethylation of HLA-C strongly correlates with hemizygous deletion of a 9 ;cM interval on 1p35-36.1, suggesting that this region encodes a modifier of ;methylation for HLA-C. ;[639..644]:gene-rna:"HLA-C" ;[671..690]:variation-type:"hemizygous deletion" ;[713..722]:variation-location:"1p35-36.1" ;[791..796]:gene-rna:"HLA-C" (SENT (S (NP-SBJ (NP (NN:[620..635] Hypomethylation)) (PP (IN:[636..638] of) (NP (NN:[639..644] HLA-C)))) (ADVP (RB:[645..653] strongly)) (VP (VBZ:[654..664] correlates) (PP-CLR (IN:[666..670] with) (NP (NP (JJ:[671..681] hemizygous) (NN:[682..690] deletion)) (PP (IN:[691..693] of) (NP (DT:[694..695] a) (NML (CD:[696..697] 9) (NN:[698..700] cM)) (NN:[701..709] interval))) (PP (IN:[710..712] on) (NP (NN:[713..715] 1p) (CD:[715..717] 35) (HYPH:[717..718] -) (CD:[718..722] 36.1))))) (,:[722..723] ,) (S-ADV (NP-SBJ (-NONE-:[723..723] *)) (VP (VBG:[724..734] suggesting) (SBAR (IN:[735..739] that) (S (NP-SBJ (DT:[740..744] this) (NN:[746..752] region)) (VP (VBZ:[753..760] encodes) (NP (NP (DT:[761..762] a) (NN:[763..771] modifier)) (PP (IN:[772..774] of) (NP (NP (NN:[775..786] methylation)) (PP (IN:[787..790] for) (NP (NN:[791..796] HLA-C)))))))))))) (.:[796..797] .))) ;sentence 8 Span:798..977 ;To test whether hypomethylation of class I HLA genes results from loss of a ;modifier gene, we fused a hypomethylating neuroblastoma cell line with a ;hypermethylating cell line. ;[834..845]:gene-rna:"class I HLA" ;[918..931]:malignancy-type:"neuroblastoma" (SENT (S (S-PRP (NP-SBJ (-NONE-:[798..798] *)) (VP (TO:[798..800] To) (VP (VB:[801..805] test) (SBAR (IN:[806..813] whether) (S (NP-SBJ (NP (NN:[815..830] hypomethylation)) (PP (IN:[831..833] of) (NP (NML (NN:[834..839] class) (CD:[840..841] I)) (NN:[842..845] HLA) (NNS:[846..851] genes)))) (VP (VBZ:[852..859] results) (PP (IN:[860..864] from) (NP (NP (NN:[865..869] loss)) (PP (IN:[870..872] of) (NP (DT:[873..874] a) (NN:[875..883] modifier) (NN:[884..888] gene))))))))))) (,:[888..889] ,) (NP-SBJ (PRP:[890..892] we)) (VP (VBD:[894..899] fused) (NP (DT:[900..901] a) (VBG:[902..917] hypomethylating) (NN:[918..931] neuroblastoma) (NN:[932..936] cell) (NN:[937..941] line)) (PP (IN:[942..946] with) (NP (DT:[947..948] a) (VBG:[949..965] hypermethylating) (NN:[966..970] cell) (NN:[972..976] line)))) (.:[976..977] .))) ;sentence 9 Span:978..1038 ;Methylation of class I HLA genes was induced in the hybrids. ;[993..1004]:gene-rna:"class I HLA" (SENT (S (NP-SBJ-1 (NP (NN:[978..989] Methylation)) (PP (IN:[990..992] of) (NP (NML (NN:[993..998] class) (CD:[999..1000] I)) (NN:[1001..1004] HLA) (NNS:[1005..1010] genes)))) (VP (VBD:[1011..1014] was) (VP (VBN:[1015..1022] induced) (NP-1 (-NONE-:[1022..1022] *)) (PP (IN:[1023..1025] in) (NP (DT:[1026..1029] the) (NNS:[1030..1037] hybrids))))) (.:[1037..1038] .))) ;sentence 10 Span:1039..1172 ;Furthermore, methylation of HLA-C, -E and -A genes, which are encoded in a ;1.4 Mb region on 6p21, is correlated in most cell lines. ;[1068..1073]:gene-rna:"HLA-C" ;[1068..1071]...[1082..1084]:gene-rna:"HLA"..."-A" ;[1068..1071]...[1075..1077]:gene-rna:"HLA"..."-E" ;[1133..1137]:variation-location:"6p21" (SENT (S (ADVP (RB:[1039..1050] Furthermore)) (,:[1050..1051] ,) (NP-SBJ-4 (NP (NN:[1053..1064] methylation)) (PP (IN:[1065..1067] of) (NP (NP (NP (NML (NML-1 (NN:[1068..1071] HLA)) (HYPH:[1071..1072] -) (NN:[1072..1073] C)) (NML-2 (-NONE-:[1073..1073] *P*))) (,:[1073..1074] ,) (NP (NML (NML-1 (-NONE-:[1074..1074] *P*)) (HYPH:[1075..1076] -) (NN:[1076..1077] E)) (NML-2 (-NONE-:[1077..1077] *P*))) (CC:[1078..1081] and) (NP (NML (NML-1 (-NONE-:[1081..1081] *P*)) (HYPH:[1082..1083] -) (NN:[1083..1084] A)) (NML-2 (NNS:[1085..1090] genes)))) (,:[1090..1091] ,) (SBAR (WHNP-3 (WDT:[1092..1097] which)) (S (NP-SBJ-3 (-NONE-:[1097..1097] *T*)) (VP (VBP:[1098..1101] are) (VP (VBN:[1102..1109] encoded) (NP-3 (-NONE-:[1109..1109] *)) (PP-LOC (IN:[1110..1112] in) (NP (NP (DT:[1113..1114] a) (CD:[1115..1118] 1.4) (NN:[1119..1121] Mb) (NN:[1122..1128] region)) (PP-LOC (IN:[1129..1131] on) (NP (NN:[1133..1137] 6p21)))))))))))) (,:[1137..1138] ,) (VP (VBZ:[1139..1141] is) (VP (VBN:[1142..1152] correlated) (NP-4 (-NONE-:[1152..1152] *)) (PP (IN:[1153..1155] in) (NP (JJS:[1156..1160] most) (NN:[1161..1165] cell) (NNS:[1166..1171] lines))))) (.:[1171..1172] .))) ;sentence 11 Span:1173..1306 ;Our results suggest that 1p35-36.1 encodes a modifier of methylation for ;class I HLA genes, that is deleted in many neuroblastomas. ;[1198..1207]:variation-location:"1p35-36.1" ;[1247..1258]:gene-rna:"class I HLA" ;[1274..1281]:variation-type:"deleted" ;[1291..1305]:malignancy-type:"neuroblastomas" (SENT (S (NP-SBJ (PRP$:[1173..1176] Our) (NNS:[1177..1184] results)) (VP (VBP:[1185..1192] suggest) (SBAR (IN:[1193..1197] that) (S (NP-SBJ (NN:[1198..1200] 1p) (CD:[1200..1202] 35) (HYPH:[1202..1203] -) (CD:[1203..1207] 36.1)) (VP (VBZ:[1209..1216] encodes) (NP (NP (NP (DT:[1217..1218] a) (NN:[1219..1227] modifier)) (PP (IN:[1228..1230] of) (NP (NP (NN:[1231..1242] methylation)) (PP (IN:[1243..1246] for) (NP (NML (NN:[1247..1252] class) (CD:[1253..1254] I)) (NN:[1255..1258] HLA) (NNS:[1259..1264] genes)))))) (,:[1264..1265] ,) (SBAR (WHNP-1 (WDT:[1266..1270] that)) (S (NP-SBJ-1 (-NONE-:[1270..1270] *T*)) (VP (VBZ:[1271..1273] is) (VP (VBN:[1274..1281] deleted) (NP-1 (-NONE-:[1281..1281] *)) (PP-LOC (IN:[1282..1284] in) (NP (JJ:[1285..1289] many) (NNS:[1291..1305] neuroblastomas)))))))))))) (.:[1305..1306] .))) ;section 12 Span:1310..1354 ;PMID: 8852654 [PubMed - indexed for MEDLINE] (SEC (FRAG (NNP:[1310..1314] PMID) (::[1314..1315] :) (CD:[1316..1323] 8852654) (NN:[1324..1325] -LSB-) (NNP:[1325..1331] PubMed) (::[1332..1333] -) (NN:[1334..1341] indexed) (IN:[1342..1345] for) (NNP:[1346..1354] MEDLINE-RSB-)))