High-resolution analysis of genomic alterations and human papillomavirus integration in anal intraepithelial neoplasia.
Anal intraepithelial neoplasia (AIN) is the likely precursor to anal cancer. AIN is associated with human papillomavirus (HPV) infection, and HPV-associated genomic instability may play an important role in the progression of squamous intraepithelial neoplasia to cancer. Microarray-based comparative genome hybridization (aCGH) was performed on DNA from AIN specimens to determine the host genomic alterations and their correlation with HPV DNA integration or rearrangement. Of 27 high-grade AIN specimens tested by CGH, 8 (30%) showed regional DNA copy number abnormalities (CNAs). Five additional cases previously identified by chromosome CGH to carry CNAs were reanalyzed by aCGH and pooled with the 8 new cases for analysis. The most common regions of gain were on chromosome arms 1p, 1q, 3q, 8p, and 20q. The most common regions of loss were on chromosome arms 2q, 7q, 11p, 11q, and 15q. HPV16 DNA integration or rearrangement correlated with CNAs in host cell DNA (P = 0.007). Although aCGH can resolve amplicons at the 1- to 2-megabase (Mb) regional resolution, the most common alteration on chromosome 3 could only be resolved to a 75-Mb region from 3q21 to qtel. Our data suggest that there may be several oncogenes in this region that are coactivated to contribute to progression to high-grade AIN.
Gagne
S Eric
SE
Comprehensive Cancer Center, Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA 94143-0126, USA.
Jensen
Ronald
R
Polvi
Anne
A
Da Costa
Maria
M
Ginzinger
David
D
Efird
Jimmy T
JT
Holly
Elizabeth A
EA
Darragh
Tere
T
Palefsky
Joel M
JM
D001005:Anus Neoplasms / Q000821:virology*; D002278:Carcinoma in Situ / Q000821:virology*; D016679:Genome, Viral; D006801:Humans; D008297:Male; D009693:Nucleic Acid Hybridization; D027383:Papillomaviridae / Q000235:genetics / Q000502:physiology*; D016662:Virus Integration