Association between cyclin D1 (CCND1) gene amplification and human papillomavirus infection in human laryngeal squamous cell carcinoma.
Head and neck squamous cell carcinomas (SCCs) seem to follow a multistep process of carcinogenesis in which chemical and/or viral agents are associated with specific genetic alterations. The prevalence of human papillomavirus (HPV) infection and the amplification of the cyclin D1 (CCND1) gene were evaluated in a series of 75 laryngeal SCCs by PCR with HPV consensus primers and Southern blot analysis with a CCND1-specific probe, respectively. HPV DNA was detected in 22 of 75 (29.3%) tumors, and it belonged almost exclusively to the highly oncogenic HPV-16, HPV-18, and HPV-33. CCND1 gene amplification was found in 15 of 75 (20%) tumors, and it was associated with HPV infection in a statistically significant manner (chi2 = 20.3; P < 0.001). Because the viral oncoproteins E6 and E7 from high-risk HPV types are known to promote genomic rearrangements, these findings suggest that amplification of the CCND1 gene in laryngeal SCCs may occur as a consequence of the genomic instability associated with HPV infection. In turn, amplified CCND1, either alone or in conjunction with a direct action of the viral oncoproteins E6 and E7, could lead to a perturbation of the cell cycle. This model could explain the involvement of high-risk HPV types in laryngeal carcinogenesis.
Cattani
P
P
Institute of Microbiology, Catholic University Medical School, Rome, Italy. ibimb@rm.unicatt.it
Hohaus
S
S
Bellacosa
A
A
Genuardi
M
M
Cavallo
S
S
Rovella
V
V
Almadori
G
G
Cadoni
G
G
Galli
J
J
Maurizi
M
M
Fadda
G
G
Neri
G
G
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000821:virology*; D019938:Cyclin D1 / Q000235:genetics*; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D005784:Gene Amplification; D006801:Humans; D007822:Laryngeal Neoplasms / Q000150:complications* / Q000235:genetics / Q000821:virology; D008297:Male; D008875:Middle Aged; D027383:Papillomaviridae / Q000235:genetics / Q000302:isolation & purification; D030361:Papillomavirus Infections / Q000150:complications* / Q000821:virology; D014412:Tumor Virus Infections / Q000150:complications* / Q000821:virology
D004279:DNA, Viral; D019938:Cyclin D1