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L1 and HERV-W retrotransposons are hypomethylated in human ovarian carcinomas.

ABSTRACT: Wide-spread hypomethylation of CpG dinucleotides is characteristic of many cancers. Retrotransposons have been identified as potential targets of hypomethylation during cellular transformation. We report the results of an preliminary examination of the methylation status of CpG dinucleotides associated with the L1 and HERV-W retrotransposons in benign and malignant human ovarian tumors. We find a reduction in the methylation of CpG dinucleotides within the promoter regions of these retroelements in malignant relative to non-malignant ovarian tissues. Consistent with these results, we find that relative L1 and HERV-W expression levels are elevated in representative samples of malignant vs. non-malignant ovarian tissues.

SUBMITTER: Menendez L

PROVIDER: S-EPMC411053 | biostudies-literature | 2004 Apr

REPOSITORIES: biostudies-literature

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L1 and HERV-W retrotransposons are hypomethylated in human ovarian carcinomas.

Menendez Laura L Benigno Benedict B BB McDonald John F JF

Molecular cancer 20040426

Wide-spread hypomethylation of CpG dinucleotides is characteristic of many cancers. Retrotransposons have been identified as potential targets of hypomethylation during cellular transformation. We report the results of an preliminary examination of the methylation status of CpG dinucleotides associated with the L1 and HERV-W retrotransposons in benign and malignant human ovarian tumors. We find a reduction in the methylation of CpG dinucleotides within the promoter regions of these retroelements ...[more]

PMID: 15109395

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Project description:BACKGROUND: It is known that all tumors studied in sufficient number to draw conclusions show characteristic/specific chromosomal rearrangements, and the identification of these chromosomes and the genes rearranged behind the aberrations may ultimately lead to a tailor-made therapy for each cancer patient. Knowledge about the acquired genomic aberrations of ovarian carcinomas is still unsatisfactory. METHODS: We cytogenetically analyzed 110 new cases of ovarian carcinoma of different histological subtypes using karyotyping of G-banded chromosomes and high-resolution comparative genomic hybridization. We first compared the aberration patterns identified by the two genomic screening techniques using the so-called "classical" pathological classification in which the carcinomas are grouped as tumors of types I and II. We also broke down our findings according to the more "modern" classification which groups the carcinomas in five different categories. RESULTS: The chromosomal breakpoints identified by karyotyping tended to cluster to 19p/q and to 11q, but no unquestionably recurrent rearrangement could be seen. Common imbalances were scored as gains from 1q, 3q, 7q, and 8q and losses from 17p, 19q, and 22q. Gain of material from 8q23 and losses from 19q and 22q have previously been described at high frequencies in bilateral and borderline ovarian carcinomas. The fact that they were present both in "precursor" lesions, i.e., borderline tumors, as well as in tumors of more advanced stages, i.e., carcinomas, highlights the possibility of an adenoma-carcinoma sequence in ovarian carcinogenesis. CONCLUSION: Based on the relatively simple genomic changes we identified in the low-grade serous carcinomas examined (n = 7) and which largely corresponded to the aberration pattern formerly identified in borderline tumors, one can interpret the cytogenetic data as supporting the view that the low-grade carcinomas represent a phenotypically more advanced stage of borderline tumors. Whether transition from low-grade to high-grade carcinoma also occurs, is a question about which the genomic data is still inconclusive.

Dataset Information

L1 and HERV-W retrotransposons are hypomethylated in human ovarian carcinomas.

Publications

L1 and HERV-W retrotransposons are hypomethylated in human ovarian carcinomas.

Similar Datasets

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