PMID- 17054308
OWN - NLM
STAT- MEDLINE
DCOM- 20070117
LR  - 20240104
IS  - 0022-3417 (Print)
IS  - 0022-3417 (Linking)
VI  - 210
IP  - 4
DP  - 2006 Dec
TI  - Genomic integration of oncogenic HPV and gain of the human telomerase gene TERC 
      at 3q26 are strongly associated events in the progression of uterine cervical 
      dysplasia to invasive cancer.
PG  - 412-9
AB  - Recently proposed events associated with the progression of cervical 
      intraepithelial neoplasia (CIN) 2/3 to cervical carcinoma include integration of 
      human papillomavirus (HPV) into the host genome, genomic instability, and an 
      increase in chromosome 3q copy number. In particular, the gene coding for the RNA 
      component of telomerase (TERC) at 3q26 has been implicated as a possible 
      candidate gene. Since it is not known to date how these events are temporally 
      related during cervical carcinogenesis, the aim of the present study was to 
      assess the correlation between TERC gene copy number and the physical status of 
      HPV during progression in cervical neoplasia. Solitary precursor lesions of the 
      uterine cervix (CIN 2/3, n = 17), lesions associated with a micro-invasive 
      carcinoma (CIN 3&mCA, n = 13), and advanced invasive carcinomas (invCA, n = 7) 
      were analysed by fluorescence in situ hybridization (FISH) to determine the 
      physical status of the virus and TERC gene copy number. The TERC gene was 
      increasingly gained with progression of CIN 2/3 (3 of 17) through CIN 3&mCA (7 of 
      13) to invCA (5 of 7). In the lesions exhibiting gain of TERC, the virus was 
      predominantly integrated. This was seen in eight of ten diploid lesions, 
      indicating that these events can occur prior to aneuploidization and are strongly 
      associated with the progression of CIN 3 to mCA and invCA (p < 0.001). With 
      progression to carcinoma, a number of these lesions show polyploidization, 
      resulting in aneuploidy and high TERC gene copy numbers. In conclusion, genomic 
      integration of oncogenic HPV and gain of the human telomerase gene TERC appear to 
      be important associated genetic events in the progression of uterine cervical 
      dysplasia to invasive cancer.
FAU - Hopman, A H N
AU  - Hopman AH
AD  - Department of Molecular Cell Biology, Research Institute Growth & Development 
      (GROW), University of Maastricht, The Netherlands. Hopman@molcelb.unimaas.nl
FAU - Theelen, W
AU  - Theelen W
FAU - Hommelberg, P P H
AU  - Hommelberg PP
FAU - Kamps, M A F
AU  - Kamps MA
FAU - Herrington, C S
AU  - Herrington CS
FAU - Morrison, L E
AU  - Morrison LE
FAU - Speel, E-J M
AU  - Speel EJ
FAU - Smedts, F
AU  - Smedts F
FAU - Ramaekers, F C S
AU  - Ramaekers FC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Pathol
JT  - The Journal of pathology
JID - 0204634
RN  - 0 (DNA, Neoplasm)
RN  - 0 (telomerase RNA)
RN  - 63231-63-0 (RNA)
RN  - EC 2.7.7.49 (Telomerase)
SB  - IM
MH  - Cell Transformation, Neoplastic/genetics/pathology
MH  - Centromere/genetics
MH  - Cervix Uteri/pathology
MH  - Chromosome Aberrations
MH  - Chromosomes, Human, Pair 3/genetics
MH  - Chromosomes, Human, Pair 7/genetics
MH  - DNA, Neoplasm/genetics
MH  - Female
MH  - Gene Amplification/genetics
MH  - Humans
MH  - In Situ Hybridization, Fluorescence/methods
MH  - Neoplasm Invasiveness
MH  - Papillomaviridae/*genetics
MH  - Ploidies
MH  - RNA/*genetics
MH  - Telomerase/*genetics
MH  - Uterine Cervical Neoplasms/*genetics/pathology
MH  - Uterine Cervical Dysplasia/*genetics/pathology
EDAT- 2006/10/21 09:00
MHDA- 2007/01/18 09:00
CRDT- 2006/10/21 09:00
PHST- 2006/10/21 09:00 [pubmed]
PHST- 2007/01/18 09:00 [medline]
PHST- 2006/10/21 09:00 [entrez]
AID - 10.1002/path.2070 [doi]
PST - ppublish
SO  - J Pathol. 2006 Dec;210(4):412-9. doi: 10.1002/path.2070.