;PMID: 9655301 ;source_file_1218.mrg ;Release 0.9 of PennBioIE ;Funded by NSF ITR EIA-0205448 ;0)section:[e:0..30] = [t:0..30] ;1)sentence:[e:35..242] = [t:35..242] ;2)section:[e:246..307] = [t:246..307] ;3)section:[e:311..393] = [t:311..393] ;4)sentence:[e:397..408] = [t:397..408] ;5)sentence:[e:409..517] = [t:409..517] ;6)sentence:[e:518..677] = [t:518..677] ;7)sentence:[e:678..777] = [t:678..777] ;8)sentence:[e:778..948] = [t:778..948] ;9)sentence:[e:950..958] = [t:950..958] ;10)sentence:[e:959..1129] = [t:959..1129] ;11)sentence:[e:1130..1209] = [t:1130..1209] ;12)sentence:[e:1210..1218] = [t:1210..1218] ;13)sentence:[e:1219..1364] = [t:1219..1364] ;14)sentence:[e:1365..1462] = [t:1365..1462] ;15)sentence:[e:1463..1625] = [t:1463..1625] ;16)sentence:[e:1626..1638] = [t:1626..1638] ;17)sentence:[e:1639..1780] = [t:1639..1780] ;18)sentence:[e:1781..2034] = [t:1781..2034] ;19)sentence:[e:2035..2234] = [t:2035..2234] ;20)section:[e:2238..2282] = [t:2238..2282] ;section 0 Span:0..30 ;Cancer 1998 Jul 1;83(1):122-9 (SEC (FRAG (NNP:[0..6] Cancer) (CD:[8..12] 1998) (NNP:[13..16] Jul) (CC:[17..22] 1;83-LRB-) (CD:[22..23] 1) (-RRB-:[23..24] -RRB-) (CD:[24..28] :122) (::[28..29] -) (CD:[29..30] 9))) ;sentence 1 Span:35..242 ;A c-rasHa mutation in the metastasis of a human papillomavirus (HPV)-18 ;positive penile squamous cell carcinoma suggests a cooperative effect ;between HPV-18 and c-rasHa activation in malignant progression. ;[37..44]:gene-rna:"c-rasHa" ;[117..147]:malignancy:"penile squamous cell carcinoma" ;[198..205]:gene-rna:"c-rasHa" (SENT (S-HLN (NP-SBJ (NP (DT:[35..36] A) (NN:[37..44] c-rasHa) (NN:[45..53] mutation)) (PP (IN:[54..56] in) (NP (NP (DT:[57..60] the) (NN:[61..71] metastasis)) (PP (IN:[72..74] of) (NP (DT:[75..76] a) (ADJP (NML (NML (NML (JJ:[77..82] human) (NN:[83..97] papillomavirus)) (NML (-LRB-:[98..99] -LRB-) (NN:[99..102] HPV) (-RRB-:[102..103] -RRB-))) (HYPH:[103..104] -) (CD:[104..106] 18)) (JJ:[107..115] positive)) (JJ:[117..123] penile) (NML (JJ:[124..132] squamous) (NN:[133..137] cell)) (NN:[138..147] carcinoma)))))) (VP (VBZ:[148..156] suggests) (NP (NP (DT:[157..158] a) (JJ:[159..170] cooperative) (NN:[171..177] effect)) (PP (IN:[178..185] between) (NP (NP (NN:[186..192] HPV-18) (NML-1 (-NONE-:[192..192] *P*))) (CC:[193..196] and) (NP (NN:[198..205] c-rasHa) (NML-1 (NN:[206..216] activation))))) (PP (IN:[217..219] in) (NP (JJ:[220..229] malignant) (NN:[230..241] progression))))) (.:[241..242] .))) ;section 2 Span:246..307 ;Leis PF, Stevens KR, Baer SC, Kadmon D, Goldberg LH, Wang XJ. (SEC (FRAG (NNP:[246..250] Leis) (NNP:[251..253] PF) (,:[253..254] ,) (NNP:[255..262] Stevens) (NNP:[263..265] KR) (,:[265..266] ,) (NNP:[267..271] Baer) (NNP:[272..274] SC) (,:[274..275] ,) (NNP:[276..282] Kadmon) (NNP:[283..284] D) (,:[284..285] ,) (NNP:[286..294] Goldberg) (NNP:[295..297] LH) (,:[297..298] ,) (NNP:[299..303] Wang) (NNP:[304..306] XJ) (.:[306..307] .))) ;section 3 Span:311..393 ;Department of Dermatology, Baylor College of Medicine, Houston, Texas 77030, ;USA. (SEC (FRAG (NNP:[311..321] Department) (IN:[322..324] of) (NNP:[325..336] Dermatology) (,:[336..337] ,) (NNP:[338..344] Baylor) (NNP:[345..352] College) (IN:[353..355] of) (NNP:[356..364] Medicine) (,:[364..365] ,) (NNP:[366..373] Houston) (,:[373..374] ,) (NNP:[375..380] Texas) (NNP:[381..386] 77030) (,:[386..387] ,) (NNP:[389..392] USA) (.:[392..393] .))) ;sentence 4 Span:397..408 ;BACKGROUND: (SENT (NP (NN:[397..407] BACKGROUND) (::[407..408] :))) ;sentence 5 Span:409..517 ;Human papillomaviruses (HPV) have been implicated in the etiology of ;anogenital squamous epithelial tumors. ;[479..516]:malignancy:"anogenital squamous epithelial tumors" (SENT (S (NP-SBJ-1 (NP (JJ:[409..414] Human) (NNS:[415..431] papillomaviruses)) (NP (-LRB-:[432..433] -LRB-) (NN:[433..436] HPV) (-RRB-:[436..437] -RRB-))) (VP (VBP:[438..442] have) (VP (VBN:[443..447] been) (VP (VBN:[448..458] implicated) (NP-1 (-NONE-:[458..458] *)) (PP (IN:[459..461] in) (NP (NP (DT:[462..465] the) (NN:[466..474] etiology)) (PP (IN:[475..477] of) (NP (JJ:[479..489] anogenital) (JJ:[490..498] squamous) (JJ:[499..509] epithelial) (NNS:[510..516] tumors)))))))) (.:[516..517] .))) ;sentence 6 Span:518..677 ;Of the 65 HPV strains, subtypes HPV-16 and HPV-18 frequently are associated ;with malignant conditions and are capable of transforming keratinocytes in ;vitro. (SENT (S (PP-TPC-1 (IN:[518..520] Of) (NP (DT:[521..524] the) (CD:[525..527] 65) (NN:[528..531] HPV) (NNS:[532..539] strains))) (,:[539..540] ,) (NP-SBJ-2 (NP (NP (NML-3 (NNS:[541..549] subtypes)) (NN:[550..556] HPV-16)) (CC:[558..561] and) (NP (NML-3 (-NONE-:[561..561] *P*)) (NN:[562..568] HPV-18))) (PP-1 (-NONE-:[568..568] *T*))) (ADVP-TMP (RB:[569..579] frequently)) (VP (VP (VBP:[580..583] are) (VP (VBN:[584..594] associated) (NP-2 (-NONE-:[594..594] *)) (PP-CLR (IN:[595..599] with) (NP (JJ:[600..609] malignant) (NNS:[610..620] conditions))))) (CC:[621..624] and) (VP (VBP:[625..628] are) (ADJP-PRD (JJ:[629..636] capable) (PP (IN:[638..640] of) (NP (VBG:[641..653] transforming) (NNS:[654..667] keratinocytes)))) (ADVP (FW:[668..670] in) (FW:[671..676] vitro)))) (.:[676..677] .))) ;sentence 7 Span:678..777 ;However, additional cellular changes are necessary to confer tumorigenicity ;to HPV-infected cells. (SENT (S (ADVP (RB:[678..685] However)) (,:[685..686] ,) (NP-SBJ-1 (JJ:[687..697] additional) (JJ:[698..706] cellular) (NNS:[707..714] changes)) (VP (VBP:[715..718] are) (ADJP-PRD (JJ:[720..729] necessary) (S (NP-SBJ-1 (-NONE-:[729..729] *)) (VP (TO:[730..732] to) (VP (VB:[733..739] confer) (NP (NN:[740..754] tumorigenicity)) (PP (TO:[755..757] to) (NP (ADJP (NN:[758..761] HPV) (HYPH:[761..762] -) (VBN:[762..770] infected)) (NNS:[771..776] cells)))))))) (.:[776..777] .))) ;sentence 8 Span:778..948 ;Secondary events implicated in the progression to malignancy include loss of ;tumor suppressor genes such as p53 and/or activation of cellular oncogenes ;such as c-rasHa. ;[888..891]:gene-rna:"p53" ;[940..947]:gene-rna:"c-rasHa" (SENT (S (NP-SBJ (NP (JJ:[778..787] Secondary) (NNS:[788..794] events)) (VP (VBN:[796..806] implicated) (NP (-NONE-:[806..806] *)) (PP (IN:[807..809] in) (NP (NP (DT:[810..813] the) (NN:[814..825] progression)) (PP (TO:[826..828] to) (NP (NN:[829..839] malignancy))))))) (VP (VBP:[840..847] include) (NP (NP (NP (NN:[848..852] loss)) (PP (IN:[853..855] of) (NP (NP (NML (NN:[856..861] tumor) (NN:[862..872] suppressor)) (NNS:[874..879] genes)) (PP (JJ:[880..884] such) (IN:[885..887] as) (NP (NN:[888..891] p53)))))) (CC:[892..898] and/or) (NP (NP (NN:[899..909] activation)) (PP (IN:[910..912] of) (NP (NP (JJ:[913..921] cellular) (NNS:[922..931] oncogenes)) (PP (JJ:[932..936] such) (IN:[937..939] as) (NP (NN:[940..947] c-rasHa)))))))) (.:[947..948] .))) ;sentence 9 Span:950..958 ;METHODS: (SENT (NP (NNS:[950..957] METHODS) (::[957..958] :))) ;sentence 10 Span:959..1129 ;Polymerase chain reaction (PCR) was used to identify HPV-16 or HPV-18 ;genetic sequence in primary penile squamous cell carcinoma and two inguinal ;lymph node metastases. ;[959..969]:gene-protein:"Polymerase" ;[1050..1088]:malignancy:"primary penile squamous cell carcinoma" ;[1097..1128]:malignancy:"inguinal lymph node metastases" (SENT (S (NP-SBJ-1 (NP (NN:[959..969] Polymerase) (NN:[970..975] chain) (NN:[976..984] reaction)) (NP (-LRB-:[985..986] -LRB-) (NN:[986..989] PCR) (-RRB-:[989..990] -RRB-))) (VP (VBD:[991..994] was) (VP (VBN:[995..999] used) (NP-1 (-NONE-:[999..999] *)) (S-PRP (NP-SBJ (-NONE-:[999..999] *)) (VP (TO:[1000..1002] to) (VP (VB:[1003..1011] identify) (NP (NP (NN:[1012..1018] HPV-16) (NML-2 (-NONE-:[1018..1018] *P*))) (CC:[1019..1021] or) (NP (NN:[1022..1028] HPV-18) (NML-2 (JJ:[1030..1037] genetic) (NN:[1038..1046] sequence)))) (PP-LOC (IN:[1047..1049] in) (NP (NP (JJ:[1050..1057] primary) (JJ:[1058..1064] penile) (NML (JJ:[1065..1073] squamous) (NN:[1074..1078] cell)) (NN:[1079..1088] carcinoma)) (CC:[1089..1092] and) (NP (CD:[1093..1096] two) (JJ:[1097..1105] inguinal) (NML (NN:[1107..1112] lymph) (NN:[1113..1117] node)) (NNS:[1118..1128] metastases))))))))) (.:[1128..1129] .))) ;sentence 11 Span:1130..1209 ;p53 and c-rasHa loci were analyzed by sequencing of PCR-amplified genomic ;DNA. ;[1130..1133]:gene-rna:"p53" ;[1138..1145]:gene-rna:"c-rasHa" (SENT (S (NP-SBJ-2 (NP (NN:[1130..1133] p53) (NML-1 (-NONE-:[1133..1133] *P*))) (CC:[1134..1137] and) (NP (NN:[1138..1145] c-rasHa) (NML-1 (NNS:[1146..1150] loci)))) (VP (VBD:[1151..1155] were) (VP (VBN:[1156..1164] analyzed) (NP-2 (-NONE-:[1164..1164] *)) (PP-MNR (IN:[1165..1167] by) (NP (NP (NN:[1168..1178] sequencing)) (PP (IN:[1179..1181] of) (NP (ADJP (NN:[1183..1186] PCR) (HYPH:[1186..1187] -) (VBN:[1187..1196] amplified)) (JJ:[1197..1204] genomic) (NN:[1205..1208] DNA))))))) (.:[1208..1209] .))) ;sentence 12 Span:1210..1218 ;RESULTS: (SENT (NP (NNS:[1210..1217] RESULTS) (::[1217..1218] :))) ;sentence 13 Span:1219..1364 ;HPV-18 but not HPV-16 infection was found in the primary carcinoma and in ;inguinal metastases occurring 5 and 7 years after the initial lesion. ;[1269..1286]:malignancy:"primary carcinoma" ;[1294..1313]:malignancy:"inguinal metastases" ;[1349..1363]:malignancy:"initial lesion" (SENT (S (NP-SBJ-1 (NP (NN:[1219..1225] HPV-18) (NML-3 (-NONE-:[1225..1225] *P*))) (CONJP (CC:[1226..1229] but) (RB:[1230..1233] not)) (NP (NN:[1234..1240] HPV-16) (NML-3 (NN:[1241..1250] infection)))) (VP (VBD:[1251..1254] was) (VP (VBN:[1255..1260] found) (NP-1 (-NONE-:[1260..1260] *)) (PP-LOC (PP (IN:[1261..1263] in) (NP (DT:[1265..1268] the) (JJ:[1269..1276] primary) (NN:[1277..1286] carcinoma))) (CC:[1287..1290] and) (PP (IN:[1291..1293] in) (NP (NP (JJ:[1294..1302] inguinal) (NNS:[1303..1313] metastases)) (VP (VBG:[1314..1323] occurring) (NP-TMP (NP (NP (CD:[1324..1325] 5) (NML-2 (-NONE-:[1325..1325] *P*))) (CC:[1326..1329] and) (NP (CD:[1330..1331] 7) (NML-2 (NNS:[1332..1337] years)))) (PP (IN:[1338..1343] after) (NP (DT:[1345..1348] the) (JJ:[1349..1356] initial) (NN:[1357..1363] lesion)))))))))) (.:[1363..1364] .))) ;sentence 14 Span:1365..1462 ;Sequence analysis did not identify any p53 mutations in the primary ;carcinoma or its metastases. ;[1404..1407]:gene-rna:"p53" ;[1426..1443]:malignancy:"primary carcinoma" ;[1451..1461]:malignancy:"metastases" (SENT (S (NP-SBJ (NN:[1365..1373] Sequence) (NN:[1374..1382] analysis)) (VP (VBD:[1383..1386] did) (RB:[1387..1390] not) (VP (VB:[1391..1399] identify) (NP (NP (DT:[1400..1403] any) (NN:[1404..1407] p53) (NNS:[1408..1417] mutations)) (PP-LOC (IN:[1418..1420] in) (NP (NP (DT:[1421..1424] the) (JJ:[1426..1433] primary) (NN:[1434..1443] carcinoma)) (CC:[1444..1446] or) (NP (PRP$:[1447..1450] its) (NNS:[1451..1461] metastases))))))) (.:[1461..1462] .))) ;sentence 15 Span:1463..1625 ;However, although the primary lesion and the 5-year metastasis encoded ;wild-type c-rasHa, the 7-year metastasis had a missense mutation within ;c-rasHa codon 61. ;[1485..1499]:malignancy:"primary lesion" ;[1516..1526]:malignancy:"metastasis" ;[1545..1552]:gene-rna:"c-rasHa" ;[1565..1575]:malignancy:"metastasis" ;[1583..1600]:variation-type:"missense mutation" ;[1608..1615]:gene-rna:"c-rasHa" ;[1616..1624]:variation-location:"codon 61" (SENT (S (ADVP (RB:[1463..1470] However)) (,:[1470..1471] ,) (SBAR-ADV (IN:[1472..1480] although) (S (NP-SBJ (NP (DT:[1481..1484] the) (JJ:[1485..1492] primary) (NN:[1493..1499] lesion)) (CC:[1500..1503] and) (NP (DT:[1505..1508] the) (NML (CD:[1509..1510] 5) (HYPH:[1510..1511] -) (NN:[1511..1515] year)) (NN:[1516..1526] metastasis))) (VP (VBD:[1527..1534] encoded) (NP (NML (JJ:[1535..1539] wild) (HYPH:[1539..1540] -) (NN:[1540..1544] type)) (NN:[1545..1552] c-rasHa))))) (,:[1552..1553] ,) (NP-SBJ (DT:[1554..1557] the) (NML (CD:[1558..1559] 7) (HYPH:[1559..1560] -) (NN:[1560..1564] year)) (NN:[1565..1575] metastasis)) (VP (VBD:[1576..1579] had) (NP (DT:[1580..1581] a) (JJ:[1583..1591] missense) (NN:[1592..1600] mutation)) (PP (IN:[1601..1607] within) (NP (NN:[1608..1615] c-rasHa) (NN:[1616..1621] codon) (CD:[1622..1624] 61)))) (.:[1624..1625] .))) ;sentence 16 Span:1626..1638 ;CONCLUSIONS: (SENT (NP (NNS:[1626..1637] CONCLUSIONS) (::[1637..1638] :))) ;sentence 17 Span:1639..1780 ;To the authors' knowledge, this is the first report of an activating c-rasHa ;mutation associated with squamous cell carcinoma of the penis. ;[1709..1716]:gene-rna:"c-rasHa" ;[1743..1779]:malignancy:"squamous cell carcinoma of the penis" (SENT (S (PP (TO:[1639..1641] To) (NP (NP (DT:[1642..1645] the) (NNS:[1646..1653] authors) (POS:[1653..1654] ')) (NN:[1656..1665] knowledge))) (,:[1665..1666] ,) (NP-SBJ (DT:[1667..1671] this)) (VP (VBZ:[1672..1674] is) (NP-PRD (NP (DT:[1675..1678] the) (JJ:[1679..1684] first) (NN:[1685..1691] report)) (PP (IN:[1692..1694] of) (NP (NP (DT:[1695..1697] an) (VBG:[1698..1708] activating) (NN:[1709..1716] c-rasHa) (NN:[1717..1725] mutation)) (VP (VBN:[1726..1736] associated) (NP (-NONE-:[1736..1736] *)) (PP-CLR (IN:[1738..1742] with) (NP (NP (NML (JJ:[1743..1751] squamous) (NN:[1752..1756] cell)) (NN:[1757..1766] carcinoma)) (PP (IN:[1767..1769] of) (NP (DT:[1770..1773] the) (NN:[1774..1779] penis)))))))))) (.:[1779..1780] .))) ;sentence 18 Span:1781..2034 ;The presence of activated c-rasHa in the second metastasis but not in the ;first metastasis or the primary lesion suggests that activation of c-rasHa ;may be a late event in the malignant progression of HPV-18-associated penile ;squamous cell carcinoma. ;[1807..1814]:gene-rna:"c-rasHa" ;[1823..1840]:malignancy:"second metastasis" ;[1856..1872]:malignancy:"first metastasis" ;[1880..1894]:malignancy:"primary lesion" ;[1924..1931]:gene-rna:"c-rasHa" ;[2003..2033]:malignancy:"penile squamous cell carcinoma" (SENT (S (NP-SBJ (NP (DT:[1781..1784] The) (NN:[1785..1793] presence)) (PP (IN:[1794..1796] of) (NP (VBN:[1797..1806] activated) (NN:[1807..1814] c-rasHa))) (PP-LOC (PP (IN:[1815..1817] in) (NP (DT:[1819..1822] the) (JJ:[1823..1829] second) (NN:[1830..1840] metastasis))) (CONJP (CC:[1841..1844] but) (RB:[1845..1848] not)) (PP (IN:[1849..1851] in) (NP (NP (DT:[1852..1855] the) (JJ:[1856..1861] first) (NN:[1862..1872] metastasis)) (CC:[1873..1875] or) (NP (DT:[1876..1879] the) (JJ:[1880..1887] primary) (NN:[1888..1894] lesion)))))) (VP (VBZ:[1896..1904] suggests) (SBAR (IN:[1905..1909] that) (S (NP-SBJ (NP (NN:[1910..1920] activation)) (PP (IN:[1921..1923] of) (NP (NN:[1924..1931] c-rasHa)))) (VP (MD:[1932..1935] may) (VP (VB:[1936..1938] be) (NP-PRD (NP (DT:[1939..1940] a) (JJ:[1941..1945] late) (NN:[1946..1951] event)) (PP (IN:[1952..1954] in) (NP (NP (DT:[1955..1958] the) (JJ:[1959..1968] malignant) (NN:[1970..1981] progression)) (PP (IN:[1982..1984] of) (NP (ADJP (NN:[1985..1991] HPV-18) (HYPH:[1991..1992] -) (VBN:[1992..2002] associated)) (JJ:[2003..2009] penile) (NML (JJ:[2010..2018] squamous) (NN:[2019..2023] cell)) (NN:[2024..2033] carcinoma))))))))))) (.:[2033..2034] .))) ;sentence 19 Span:2035..2234 ;Analysis of additional samples from primary lesions and their resultant ;metastases is necessary to elucidate the incidence and significance of ;c-rasHa activation in penile squamous cell carcinoma. ;[2072..2087]:malignancy:"primary lesions" ;[2108..2118]:malignancy:"metastases" ;[2180..2187]:gene-rna:"c-rasHa" ;[2203..2233]:malignancy:"penile squamous cell carcinoma" (SENT (S (NP-SBJ (NP (NN:[2035..2043] Analysis)) (PP (IN:[2044..2046] of) (NP (NP (JJ:[2048..2058] additional) (NNS:[2059..2066] samples)) (PP (IN:[2067..2071] from) (NP (NP (JJ:[2072..2079] primary) (NNS:[2080..2087] lesions)) (CC:[2088..2091] and) (NP (PRP$:[2092..2097] their) (JJ:[2098..2107] resultant) (NNS:[2108..2118] metastases))))))) (VP (VBZ:[2119..2121] is) (ADJP-PRD (JJ:[2123..2132] necessary) (S (NP-SBJ (-NONE-:[2132..2132] *)) (VP (TO:[2133..2135] to) (VP (VB:[2136..2145] elucidate) (NP (NP (DT:[2146..2149] the) (NN:[2150..2159] incidence) (CC:[2160..2163] and) (NN:[2164..2176] significance)) (PP (IN:[2177..2179] of) (NP (NN:[2180..2187] c-rasHa) (NN:[2188..2198] activation))) (PP (IN:[2199..2201] in) (NP (JJ:[2203..2209] penile) (NML (JJ:[2210..2218] squamous) (NN:[2219..2223] cell)) (NN:[2224..2233] carcinoma))))))))) (.:[2233..2234] .))) ;section 20 Span:2238..2282 ;PMID: 9655301 [PubMed - indexed for MEDLINE] (SEC (FRAG (NNP:[2238..2242] PMID) (::[2242..2243] :) (CD:[2244..2251] 9655301) (NN:[2252..2253] -LSB-) (NNP:[2253..2259] PubMed) (::[2260..2261] -) (NN:[2262..2269] indexed) (IN:[2270..2273] for) (NNP:[2274..2282] MEDLINE-RSB-)))