Identification of chromosomal alterations important in the development of cervical intraepithelial neoplasia and invasive carcinoma using alignment of DNA microarray data

Abstract

Objective. To use microarray data to reveal regions of potential chromosomal loss or gain important in cervical intraepithelial neoplasia (CIN) and invasive cervical cancer by identifying mRNA expression biases in contiguous chromosomal regions. Methods. Data from three RNA expression microarray experiments were used: one primary experiment using cDNA arrays profiling gene expression in cervical epithelium from viral cytopathic effect to invasive cancer, one experiment using Affymetrix arrays profiling gene expression in invasive cancerous cervical epithelium, and one experiment using Affymetrix arrays profiling gene expression in CIN cervical biopsy specimens. Gene expression was aligned along chromosomes to reveal regions of significant chromosomal imbalance. Regions showing significant gain or loss and verified in more than one experiment are presented here. RT-PCR was performed to validate expression of one gene in a region. Results. Gain of 3q was detected from the CIN II ( P = 0.018), CIN III ( P = 0.005), and invasive cancer ( P = 0.0002) cDNA arrays, and gain of 12q was detected from the CIN ( P = 0.05) and invasive cancer ( P = 0.05) Affymetrix arrays. Loss of 6p was detected from the CIN III ( P = 0.004) cDNA arrays and invasive cancer ( P = 0.05) Affymetrix arrays. Loss of 4q was detected from the invasive cancer ( P = 0.04) cDNA arrays and invasive cancer ( P = 0.05) Affymetrix arrays. RAN, located in the region of gain on 12q24.3, was overexpressed in CIN and invasive cancer. Conclusions. Alignment of microarray expression data by chromosomes can be used to estimate regions of potential chromosomal aberration and identify differentially expressed genes important in the development of CIN and invasive cancer.