{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T14:33:48Z","timestamp":1789914828220,"version":"4.0.1"},"reference-count":66,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2004,5,11]],"date-time":"2004-05-11T00:00:00Z","timestamp":1084233600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes Chromosomes &amp; Cancer"],"published-print":{"date-parts":[[2004,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>High\u2010risk human papillomaviruses (HPVs), specifically HPV\u201016 and \u201018, have been associated with the development of carcinoma in situ (CIS) and of invasive cervical cancer (CC). However, only a small fraction of HPV\u2010infected women will show signs of disease progression, suggesting that other factors in the carcinogenic pathway are needed. We previously demonstrated that human leukocyte antigen (HLA) DRB1*1501\u2010DQB1*0602 (high risk) was associated with the development of CIS and CC tumors in HPV\u201016\u2010positive patients. To characterize the molecular changes that could be relevant to tumor progression, we compared the extent of loss of heterozygosity (LOH) on chromosome 6 in HPV\u201016\u2010positive CIS patients who were carriers of high\u2010risk and neutral HLA haplotypes. CIS and CC cases demonstrated similar LOH patterns. A wide range of LOH frequencies was found at 6p (10\u201353%) and 6q (5\u201328%) in CIS cases, suggesting that LOH is an early event in the carcinogenic process. A comparative analysis of LOH frequencies in the high\u2010risk versus the neutral HLA haplotypes showed a statistically significant difference in the extent of LOH at 6p24\u2013p25 (58.6% versus 25.8%; <jats:italic>P<\/jats:italic> = 0.018) and at 6p21.3 (79.3% versus 35.5%; <jats:italic>P<\/jats:italic> = 0.001), a region that contains the HLA complex. LOH at this region could affect genes encoding HLA class I\u2013II molecules, as well as factors responsible for the assembly, transport, and stable expression of HLA molecules. These losses may be a reflection of both an abnormal immune response and a general genome\u2010wide instability resulting from virus persistence. \u00a9 2004 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/gcc.20048","type":"journal-article","created":{"date-parts":[[2004,6,3]],"date-time":"2004-06-03T19:03:56Z","timestamp":1086289436000},"page":"277-284","source":"Crossref","is-referenced-by-count":30,"title":["Loss of heterozygosity on chromosome 6 in HPV\u201016 positive cervical carcinomas carrying the DRB1*1501\u2010DQB1*0602 haplotype"],"prefix":"10.1002","volume":"40","author":[{"given":"Hugo","family":"Arias\u2010Pulido","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy","family":"Joste","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cosette M.","family":"Wheeler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2004,5,11]]},"reference":[{"key":"e_1_2_6_2_1","first-page":"48","volume-title":"Cancer facts and figures 2002","author":"American Cancer Society (ACS)","year":"2002"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0039.1996.tb02602.x"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0294-157"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/87.6.427"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-4608(90)90052-C"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.1412"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0215(19981005)78:2<166::AID-IJC8>3.0.CO;2-X"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-0039.2000.550502.x"},{"key":"e_1_2_6_10_1","first-page":"2119","article-title":"Mapping the sites of putative tumor suppressor genes at 6p25 and 6p21.3 in cervical carcinoma: occurrence of allelic deletions in precancerous lesions","volume":"61","author":"Chatterjee A","year":"2001","journal-title":"Cancer Res"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.1994.28"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1054\/bjoc.1999.1103"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(92)92464-Q"},{"key":"e_1_2_6_14_1","first-page":"43","article-title":"The significance of human leukocyte antigen associations with cervical cancer","volume":"8","author":"Davies D","year":"1997","journal-title":"Papillomavirus Report"},{"key":"e_1_2_6_15_1","first-page":"3475","article-title":"Prognostic value of genomic alterations in invasive cervical squamous cell carcinoma of clinical stage Ib detected by comparative genomic hybridization","volume":"59","author":"Dellas A","year":"1999","journal-title":"Cancer Res."},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1205709"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm0595-464"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-0039.2000.550601.x"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-5699(96)10075-X"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1054\/bjoc.1999.0937"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0090-8258(02)00074-4"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.2910570411"},{"key":"e_1_2_6_23_1","first-page":"1079","article-title":"Loss of heterozygosity on chromosome 6p21.2 as a potential marker for recurrence after radiotherapy of human cervical cancer","volume":"6","author":"Harima Y","year":"2000","journal-title":"Clin Cancer Res"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.10158"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-72-7-1569"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.1.479"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-1702(02)00191-0"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/169.2.235"},{"key":"e_1_2_6_29_1","first-page":"1035","article-title":"Human leukocyte antigen class I\/II alleles and development of human papillomavirus\u2010related cervical neoplasia: results from a case\u2010control study conducted in the United States","volume":"7","author":"Hildesheim A","year":"1998","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/93.4.315"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0046-8177(98)90117-4"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0215(19980821)79:4<411::AID-IJC17>3.0.CO;2-7"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-2264(199912)26:4<346::AID-GCC9>3.0.CO;2-D"},{"key":"e_1_2_6_34_1","first-page":"427","article-title":"Expression of HPV16 E6 or E7 increases integration of foreign DNA","volume":"13","author":"Kessis T","year":"1996","journal-title":"Oncogene"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-4608(01)00424-1"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0215(19961220)69:6<484::AID-IJC12>3.0.CO;2-1"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-230X(01)82007-8"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/91.19.1669"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.191.6.961"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0142(19990915)86:6<997::AID-CNCR15>3.0.CO;2-Q"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0198-8859(98)00127-X"},{"key":"e_1_2_6_42_1","first-page":"859","article-title":"High resolution mapping of chromosome 6 deletions in cervical cancer","volume":"6","author":"Mazurenko N","year":"1999","journal-title":"Oncol Rep"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0029-7844(98)00245-2"},{"key":"e_1_2_6_44_1","first-page":"4481","article-title":"Allelotype analysis of cervical carcinoma","volume":"54","author":"Mitra A","year":"1994","journal-title":"Cancer Res"},{"key":"e_1_2_6_45_1","first-page":"197","article-title":"Genomic alterations in cervical carcinoma: losses of chromosome heterozygosity and human papilloma virus tumor status","volume":"56","author":"Mullokandov M","year":"1996","journal-title":"Cancer Res"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1206432"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0029-7844(99)00501-3"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF03401564"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0215(19960904)67:5<595::AID-IJC1>3.0.CO;2-P"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004347-199304000-00018"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0215(19990315)80:6<827::AID-IJC6>3.0.CO;2-P"},{"key":"e_1_2_6_52_1","first-page":"6677","article-title":"Identification of a 6\u2010cM minimal deletion at 11q23.1\u201323.2 and exclusion of PPP2R1B gene as a deletion target in cervical cancer","volume":"60","author":"Pulido HA","year":"2000","journal-title":"Cancer Res"},{"key":"e_1_2_6_53_1","first-page":"2737","article-title":"Allelotyping of all chromosomal arms in invasive cervical cancer","volume":"13","author":"Rader J","year":"1996","journal-title":"Oncogene"},{"key":"e_1_2_6_54_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-2264(199805)22:1<57::AID-GCC8>3.0.CO;2-6"},{"key":"e_1_2_6_55_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-2264(200004)27:4<373::AID-GCC6>3.0.CO;2-V"},{"key":"e_1_2_6_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0198-8859(00)00171-3"},{"key":"e_1_2_6_57_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.8.18.2227"},{"key":"e_1_2_6_58_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-2264(199907)25:3<195::AID-GCC1>3.0.CO;2-8"},{"key":"e_1_2_6_59_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0215(19960621)69:3<159::AID-IJC1>3.0.CO;2-Z"},{"key":"e_1_2_6_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(93)93044-2"},{"key":"e_1_2_6_61_1","doi-asserted-by":"publisher","DOI":"10.1086\/324209"},{"key":"e_1_2_6_62_1","doi-asserted-by":"publisher","DOI":"10.1038\/352723a0"},{"key":"e_1_2_6_63_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.8.6.666"},{"key":"e_1_2_6_64_1","first-page":"35","article-title":"Human papillomaviruses","volume":"64","author":"World Health Organization (WHO)","year":"1995","journal-title":"IARC Monogr Eval Carcinog Risks Hum"},{"key":"e_1_2_6_65_1","first-page":"6027","article-title":"A prospective study showing long\u2010term infection with human papillomavirus 16 before the development of cervical carcinoma in situ","volume":"60","author":"Ylitalo N","year":"2000","journal-title":"Cancer Res"},{"key":"e_1_2_6_66_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.1520"},{"key":"e_1_2_6_67_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/92.9.690"}],"container-title":["Genes, Chromosomes and Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fgcc.20048","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/gcc.20048","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T09:24:10Z","timestamp":1697016250000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/gcc.20048"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,5,11]]},"references-count":66,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2004,8]]}},"alternative-id":["10.1002\/gcc.20048"],"URL":"https:\/\/doi.org\/10.1002\/gcc.20048","archive":["Portico"],"relation":{},"ISSN":["1045-2257","1098-2264"],"issn-type":[{"value":"1045-2257","type":"print"},{"value":"1098-2264","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,5,11]]}}}