Korean J Pathol.  2012 Apr;46(2):123-130.

Difference of Genome-Wide Copy Number Alterations between High-Grade Squamous Intraepithelial Lesions and Squamous Cell Carcinomas of the Uterine Cervix

• Lee BH
• Roh S
• Kim YI
• Lee A
• Kim SY

Abstract

BACKGROUND
About 10% of high-grade squamous intraepithelial lesions (HSILs) progress to invasive carcinomas within 2-10 years. By delineating the events that occur in the early stage of the invasion, the pathogenesis of cervical cancer could be better understood. This will also propose the possible methods for inhibiting the tumor invasion and improving the survival of patients.
METHODS
We compared the genomic profiles between the HSIL and the invasive squamous cell carcinoma (SCC) using an array comparative genomic hybridization. Using recurrently altered genes, we performed a principal component analysis to see variation of samples in both groups. To find possibly affected pathways by altered genes, we analyzed genomic profiles with the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database and GOEAST software.
RESULTS
We found 11q12.3 and 2p24.1 regions have recurrent copy number gains in both groups. 16p12-13 and 20q11-13 regions showed an increased copy number only in cases of HSIL. 1q25.3 and 3q23-29 regions showed copy number gains only in cases of SCC. Altered genes in the SCC group were related to the mitogen-activated protein kinase signaling pathway and the RNA transport. Altered genes in the HSIL group were related to the ubiquitin mediated proteolysis and cell adhesion molecules.
CONCLUSIONS
Our results showed not only that gains in 11q12.3 and 2p24.1 were early events occurring in the premalignant lesions and then maintained in cases of SCC but also that gains in 1q25.3 and 3q23-29 were late events occurring after invasion in those of SCC.

Keyword

Gene dosage; DNA copy number variations; Carcinoma, squamous cell; Cervical intraepithelial neoplasia

MeSH Terms

Carcinoma, Squamous Cell
Cell Adhesion
Cervical Intraepithelial Neoplasia
Cervix Uteri
Coat Protein Complex I
Comparative Genomic Hybridization
DNA Copy Number Variations
Female
Gene Dosage
Genome
Principal Component Analysis
Protein Kinases
Proteolysis
RNA Transport
Ubiquitin
Uterine Cervical Neoplasms
Coat Protein Complex I
Protein Kinases
Ubiquitin