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Cervical neoplasia genomes

ABSTRACT: Cervical intraepithelial neoplasia (CIN), also known as cervical dysplasia, is premalignant lesions of the cervical squamous cell carcinoma (CSCC) that shows abnormal growth of squamous cells in the cervix epithelium. Given the evidence suggesting that differences may exist between CIN and CSCC, we hypothesize that progression may be mediated by subpopulation selection or by acquisition of additional alterations, including gene mutations or chromosomal alterations. In this study, we analyzed cervical CIN, microinvasive carcinoma (MIC) and CSCC by whole-exome sequencing and array-comparative genomic hybridization (array-CGH) and found that CIN genomes harbored fewer mutations (especially fewer driver mutations) and copy number alterations (CNAs), suggesting that additional genomic alterations might burst onto the CIN genome at the final stage of CIN progression to CSCC or an early stage of CSCC.

ORGANISM(S): Homo sapiens

PROVIDER: GSE60067 | GEO | 2014/12/31

SECONDARY ACCESSION(S): PRJNA257407

REPOSITORIES: GEO

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Project description:Background. MicroRNAs (miRNAs) are short (~22 nt) non-coding regulatory RNAs that control gene expression at the translational level. Deregulation of miRNA expression has been discovered in a wide variety of tumours and it is now clear that they contribute to cancer development and progression. This prompted the development of miRNA-chips for cancer diagnosis or prognosis, opening a new door to understand carcinogenesis. Cervical cancer is one of the most common cancers in women worldwide. Therefore, there is a strong need for a non-invasive, fast and efficient method to diagnose the disease. We investigated miRNA expression profiles in cervical cancer using a microarray platform developed in house containing probes for mature miRNAs. Results. We have evaluated miRNA expression profiles of a heterogeneous set of cervical tissues from 25 different patients. This set included 19 normal cervical tissues, 4 squamous cell carcinoma, 5 high-grade squamous intraepithelial lesion (HSIL) and 9 low-grade squamous intraepithelial lesion (LSIL) samples. We observed high variability in miRNA expression especially among normal cervical samples, which prevented us from obtaining a unique miRNA expression signature for this tumour type. However, miRNAs deregulation in malignant and pre-malignant cervical tissues was detected after tackling the high variability observed. We were also able to identify putative targets of relevant candidate miRNAs. Conclusions. Our results show that miRNA deregulation may play an important role in the malignant transformation of cervical squamous cells. In addition, deregulated miRNAs highlight new candidate targets allowing a better understanding of the molecular mechanism of this tumour type. In this study we used a common reference design experiment where the common reference used was a commercial RNA from normal cervix (Ambion) and the test samples were 4 pre-treatment squamous cell cervical carcinoma, 7 high-grade Squamous Intraepithelial Lesion (CINII, n=2 and CIN III, n=5) sample, 9 low-grade Squamous Intraepithelial Lesion (CIN I) samples, 19 normal cervix samples and 4 pools of normal cervix samples.

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Cervical neoplasia genomes

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