PMID- 15146560
OWN - NLM
STAT- MEDLINE
DCOM- 20040630
LR  - 20160303
IS  - 0020-7136 (Print)
IS  - 0020-7136 (Linking)
VI  - 110
IP  - 5
DP  - 2004 Jul 10
TI  - Mapping and analysis of HPV16 integration sites in a head and neck cancer cell 
      line.
PG  - 701-9
AB  - Human papillomavirus (HPV) is a circular double-stranded DNA virus implicated in 
      at least 90% of cervical and anogenital cancers and has been observed in 
      approximately 20% of squamous cell carcinomas of the head and neck (SCCHN). 
      Transcription of the viral oncogenes E6 and E7 is regulated by expression of the 
      E2 protein. Disruption of the E2 gene sequence due to viral integration results 
      in upregulation of E6 and E7, which promote tumorigenesis by abrogating p53 and 
      pRb functions. HPV integration sites in cervical and anogenital cancers have been 
      mapped primarily to chromosomal fragile sites and in some cases have been shown 
      to integrate within tumor suppressor genes or other cancer-related genes. To 
      study viral integration sites in SCCHN, we examined an HPV16-infected SCCHN cell 
      line cultured from a tongue-base tumor. HPV fluorescence in situ hybridization 
      (FISH) revealed multiple integrated viral DNA copies in blocks throughout the 
      genome. Sequential FISH and spectral karyotyping identified integration sites on 
      chromosomes 3, 6, 9q, 13q and t(1;8)(q;?). Restriction site-polymerase chain 
      reaction (RS-PCR) was performed to identify the viral-cellular junctions. 
      Sequence analyses confirmed integration sites at 9q31.1 and 6p21 and revealed a 
      novel junction at 16p12.3. Subsequent chromosome breakage studies suggested that 
      the observed viral-cellular integration sites may have occurred within common 
      fragile sites. Additional studies using RT-PCR for E6--E7 viral transcripts 
      showed oncoprotein expression from episomal and integrated viral sequences. Our 
      results suggest that viral integration of HPV in SCCHN appears to occur 
      nonrandomly through targeting specific chromosomal sequences prone to breakage.
CI  - Copyright 2004 Wiley-Liss, Inc.
FAU - Ragin, Camille C Rose
AU  - Ragin CC
AD  - Department of Human Genetics, University of Pittsburgh Graduate School of Public 
      Health, Pittsburgh, PA 15261, USA.
FAU - Reshmi, Shalini C
AU  - Reshmi SC
FAU - Gollin, Susanne M
AU  - Gollin SM
LA  - eng
GR  - P30CA47904/CA/NCI NIH HHS/United States
GR  - R01DE10513/DE/NIDCR NIH HHS/United States
GR  - R25CA89507/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Int J Cancer
JT  - International journal of cancer
JID - 0042124
RN  - 0 (DNA, Viral)
RN  - 0 (E1 protein, Human papillomavirus 16)
RN  - 0 (E6 protein, Human papillomavirus type 16)
RN  - 0 (Oncogene Proteins, Viral)
RN  - 0 (Papillomavirus E7 Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Repressor Proteins)
RN  - 0 (oncogene protein E7, Human papillomavirus type 16)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Adult
MH  - Binding Sites
MH  - Carcinoma, Squamous Cell/genetics/pathology/virology
MH  - Cell Line, Tumor
MH  - Chromosome Mapping
MH  - DNA/metabolism
MH  - DNA, Viral/genetics
MH  - Head and Neck Neoplasms/genetics/pathology/*virology
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Karyotyping
MH  - Male
MH  - Models, Genetic
MH  - Oncogene Proteins, Viral/*genetics/metabolism
MH  - Papillomavirus E7 Proteins
MH  - Polymerase Chain Reaction
MH  - RNA, Messenger/metabolism
MH  - *Repressor Proteins
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Transcription, Genetic
EDAT- 2004/05/18 05:00
MHDA- 2004/07/01 05:00
CRDT- 2004/05/18 05:00
PHST- 2004/05/18 05:00 [pubmed]
PHST- 2004/07/01 05:00 [medline]
PHST- 2004/05/18 05:00 [entrez]
AID - 10.1002/ijc.20193 [doi]
PST - ppublish
SO  - Int J Cancer. 2004 Jul 10;110(5):701-9. doi: 10.1002/ijc.20193.