Demonstration of somatic rearrangements and genomic heterogeneity in human ovarian cancer by DNA fingerprinting

E M Boltz, P Harnett, J Leary, R Houghton, R F Kefford, M L Friedlander
British journal of cancer · 1990 · doi:10.1038/bjc.1990.222 · PMID:2390478 · PMC1971745
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DNA fingerprinting revealed somatic changes, including loss of heterozygosity, in 70% of ovarian tumors and demonstrated genomic heterogeneity across different tumor sites within individual patients.

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The paper analyzed DNA from 14 patients with epithelial ovarian tumours to detect somatic genomic rearrangements and assess how frequently clonal changes occur during metastasis and progression, using satellite DNA probes (33.15, 228S, 216S) and DNA fingerprinting. Somatic changes were detected in about 70% of tumours, most commonly as band deletion or reduced intensity consistent with loss of heterozygosity, along with increased band intensification and novel DNA fragments; restriction enzyme digestion indicated that methylation differences alone could not explain all changes. Tumours showed genomic heterogeneity, with different DNA patterns in different sites in five of eight patients, while within individual patients primary and metastases generally shared a common fingerprint pattern with minor site-specific variations. The authors conclude DNA fingerprint analysis is sensitive for detecting somatic changes and investigating clonal heterogeneity. This paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.

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Abstract

A detailed study was performed in 14 patients with epithelial ovarian tumours using the satellite probes 33.15, 228S and 216S to investigate the nature of somatic changes and frequency with which clonal changes could be demonstrated during metastasis and progression. Somatic changes were evident in approximately 70% of ovarian tumours, the most common being a deletion or reduction in intensity of a band suggesting loss of heterozygosity. Additional changes that were observed included increased intensification of single bands and the appearance of novel DNA fragments. Somatic alterations were seen following digestion of DNA with methylation resistant restriction endonucleases indicating that methylation differences alone could not account for all of the somatic changes. Using DNA fingerprint analysis ovarian tumours were shown to be heterogeneous with different DNA patterns observed in different sites in five of eight patients. Generally, within an individual patient the primary and metastases appeared to share a DNA fingerprint pattern with minor variations occurring in different sites suggesting that different populations have derived from a common stem line. This study clearly demonstrates that DNA fingerprint analysis is a sensitive method to detect somatic changes in tumour DNA and for investigating the development of clonal heterogeneity in ovarian tumours.
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Abstract A detailed study was performed in 14 patients with epithelial ovarian tumours using the satellite probes 33.15, 228S and 216S to investigate the nature of somatic changes and frequency with which clonal changes could be demonstrated during metastasis and progression. Somatic changes were evident in approximately 70% of ovarian tumours, the most common being a deletion or reduction in intensity of a band suggesting loss of heterozygosity. Additional changes that were observed included increased intensification of single bands and the appearance of novel DNA fragments. Somatic alterations were seen following digestion of DNA with methylation resistant restriction endonucleases indicating that methylation differences alone could not account for all of the somatic changes. Using DNA fingerprint analysis ovarian tumours were shown to be heterogeneous with different DNA patterns observed in different sites in five of eight patients. Generally, within an individual patient the primary and metastases appeared to share a DNA fingerprint pattern with minor variations occurring in different sites suggesting that different populations have derived from a common stem line. This study clearly demonstrates that DNA fingerprint analysis is a sensitive method to detect somatic changes in tumour DNA and for investigating the development of clonal heterogeneity in ovarian tumours. This is a preview of subscription content, access via your institution Access options Subscribe to this journal Receive 24 print issues and online access 251,40 € per year only 10,48 € per issue Buy this article - Purchase on SpringerLink - Instant access to the full article PDF. 39,95 € Prices may be subject to local taxes which are calculated during checkout Similar content being viewed by others Author information Authors and Affiliations Rights and permissions About this article Cite this article Boltz, E., Harnett, P., Leary, J. et al. Demonstration of somatic rearrangements and genomic heterogeneity in human ovarian cancer by DNA fingerprinting. Br J Cancer 62, 23–27 (1990). https://doi.org/10.1038/bjc.1990.222 Issue date: DOI: https://doi.org/10.1038/bjc.1990.222 This article is cited by - Application of highly polymorphic dna markers to the identification of hela cell sublines In Vitro Cellular & Developmental Biology - Animal (1992)

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endometriosis

MeSH descriptors

Chromosome Aberrations Ovarian Neoplasms Adenocarcinoma Adenocarcinoma Cystadenocarcinoma Cystadenocarcinoma DNA Probes DNA, Satellite DNA, Satellite Endometriosis Endometriosis Female Fibroma Fibroma Humans Neoplasm Metastasis Neoplasm Metastasis Nucleotide Mapping Ovarian Neoplasms Rectal Neoplasms

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