Differential DNA copy number aberrations in the progression of cervical lesions to invasive cervical carcinoma

Abstract

Host genomic alterations in addition to human papillomavirus (HPV) are needed for cervical precursor lesions to progress to invasive cancer because only a small percentage of women infected by the virus develop disease. However, the genomic alterations during the progression of cervical lesions have not been systematically examined. The aim of this study was to identify differential genomic alterations among cervical intraepithelial neoplasia CIN1, CIN2, CIN3 and cervical squamous cell carcinoma (SCC). Genomic alterations were examined for 15 cases each of CIN1, CIN2, CIN3 and SCC by array-based comparative genomic hybridization (array CGH). The chromosomal regions showing significant differential in DNA copy number aberrations (DCNAs) among CIN1, CIN2, CIN3 and SCC were successfully identified by resampling-based t-test. The chromosomal regions of 5q35.3 and 2q14.3 showed significant DCNAs between CIN1 and CIN2, and between CIN2 and CIN3, respectively, while a significant difference in DCNAs between CIN3 and SCC was observed at 1q24.3, 3p14.1, 3p14.2, 5q13.2, 7p15.3, 7q22.1 and 13q32.3. In addition, the status of DCNAs in 1q43, 2p11.2, 6p11.2, 7p21.1, 7p14.3, 10q24.1, 13q22.3, 13q34 and 16p13.3 was conserved throughout the progression of CIN to SCC. The presence of differential and common DCNAs among CIN1, CIN2, CIN3 and SCC supports that the CIN progression may include continual clonal selection and evolution. This approach also identified 34 probe sets consistently overexpressed when amplified, suggesting an unbiased identification of candidate genes in SCC during cervical cancer progression.

Genetic Variants at 6p21.1 and 7p15.3 Identified by GWASs of Multiple Cancers and Ovarian Cancer Risk: a Case-control Study in Han Chinese Women

“…Our study showed that rs2285947 A allele was associated with an increased risk of ovarian cancer risk in Han Chinese women, consistent with the findings in lung cancer, non-cardia gastric cancer, and esophageal squamous-cell carcinoma by Jin et al (2012). Furthermore, it has been reported that several other loci at 7p15.3 were associated with many kinds of cancers, such as multiple myeloma (rs4487645) (Broderick et al, 2012;Martino et al, 2012) and lung cancer (rs2710994) (Xun et al, 2011), and DNA copy number aberrations (DCNAs) at 7p15.3 increased the risk of invasive cervical carcinoma (Oh et al, 2012). All these findings provided evidence that genetic variants at 7p15.3 are potentially important susceptibility loci associated with the development of multiple cancers.…”

Genetic variants of DNAH11 and LRFN2 genes and their association with ovarian and breast cancer

“…25 It has been reported that changes in copy number variations at 7p15.3 have also been found to be associated with a risk of invasive cervical carcinoma. 26 The LRFN2 protein is a member of the SALM family that shows interaction with the N-methyld-aspartate (NMDA) receptor. 16 Methylation of the 2B receptor of NMDA has been observed to serve as a susceptible gene for multiple cancers through the LRFN2-NMDA receptor pathway.…”

MicroRNAs asociados al Cáncer de Cuello Uterino

“…Otros estudios han demostrado perfiles de expresión diferencial entre tejido normal, lesiones precursoras (NIC) y tejidos con cáncer provenientes del cuello uterino 19,20,87,93,102,128 . Wilting et al realizaron un análisis sobre los patrones de expresión de miRNAs entre tejidos cervicales normales, lesiones precursoras (NIC II, III) y tejidos cancerosos del cuello uterino, mostraron 33 miRNAs con perfiles de expresiones diferencial concordante; 18 miRNAs sobre-expresados (Let7i, miR-19b, miR-21, miR-25, miR-28-5p, miR30e, miR-34a, miR-34b*, miR-92a, miR-92b, miR106b, miR-146a, miR-181d, miR-200a*, miR-206, miR-338-5p, miR-592 y miR-595) y 15 miRNAs infra-expresados (miR-23b, miR-134, miR-149, miR-193b, miR-203, miR-210, miR-296-5p, miR-365, miR-370, miR-493, miR-572, miR-575, miR-617, miR-622 y miR-638) 51 .…”