Genomic organization of amplified MYC genes suggests distinct mechanisms of amplification in tumorigenesis.
Integration of the human papillomavirus (HPV) genome into the host genome is associated with the disruption of the HPV E2 gene and with amplification and rearrangement of the viral and flanking cellular sequences. Molecular characterization of the genomic structures of coamplified HPV sequences and oncogenes provides essential information concerning the mechanisms of amplification and their roles in carcinogenesis. Using fluorescent hybridization on stretched DNA molecules in two cervical cancer-derived cell lines, we have elucidated the genomic structures of amplified regions containing HPV/myc genes over several hundreds of kilobases. Direct visualization of hybridization signals on individual DNA molecules suggests that overreplication and breakage-fusion-bridge-type mechanisms are involved in the genomic instability associated with HPV cervical cancers. Further analysis from two other genital cancer-derived cell lines reveals a recurrent motif of amplification, probably generated by a common mechanism involving overreplication upon viral integration. Interestingly, different amplification patterns seem to be correlated with the disease outcome, thus providing new insights into HPV-related cancer development and tumor progression.
Herrick
John
J
Unité Stabilité des Génomes, Département de Structure et Dynamique des Génomes, Institut Pasteur, Paris, France.
Conti
Chiara
C
Teissier
Sebastien
S
Thierry
Francoise
F
Couturier
Jérôme
J
Sastre-Garau
Xavier
X
Favre
Michel
M
Orth
Gérard
G
Bensimon
Aaron
A
D005260:Female; D005784:Gene Amplification; D016259:Genes, myc / Q000235:genetics*; D015894:Genome, Human; D006801:Humans; D005810:Multigene Family; D009856:Oncogene Proteins, Viral / Q000235:genetics; D027383:Papillomaviridae / Q000235:genetics*; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000821:virology*; D016662:Virus Integration / Q000235:genetics
D009856:Oncogene Proteins, Viral; C069102:oncogene protein E2, Human papillomavirus type 18