Novel near-diploid ovarian cancer cell line derived from a highly aneuploid metastatic ovarian tumor
Resumen:
A new ovarian near-diploid cell line, OVDM1, was derived from a highly aneuploid serous ovarian metastatic adenocarcinoma. A metastatic tumor was obtained from a 47-year-old Ashkenazi Jewish patient three years after the first surgery removed the primary tumor, both ovaries, and the remaining reproductive organs. OVDM1 was characterized by cell morphology, genotyping, tumorigenic assay, mycoplasma testing, spectral karyotyping (SKY), and molecular profiling of the whole genome by aCGH and gene expression microarray. Targeted sequencing of a panel of cancer-related genes was also performed. Hierarchical clustering of gene expression data clearly confirmed the ovarian origin of the cell line. OVDM1 has a near-diploid karyotype with a low-level aneuploidy, but samples of the original metastatic tumor were grossly aneuploid. A number of single nucleotide variations (SNVs)/ mutations were detected in OVDM1 and the metastatic tumor samples. Some of them were cancer-related according to COSMIC and HGMD databases (no founder mutations in BRCA1 and BRCA2 have been found). A large number of focal copy number alterations (FCNAs) were detected, including homozygous deletions (HDs) targeting WWOX and GATA4. Progression of OVDM1 from early to late passages was accompanied by preservation of the near-diploid status, acquisition of only few additional large chromosomal rearrangements and more than 100 new small FCNAs. Most of newly acquired FCNAs seem to be related to localized but massive DNA fragmentation (chromothripsis-like rearrangements). Newly developed near-diploid OVDM1 cell line offers an opportunity to evaluate tumorigenesis pathways/events in a minor clone of metastatic ovarian adenocarcinoma as well as mechanisms of chromothripsis.
2017 | |
Neoplasms Mutation Intratumor heterogeneity |
|
Inglés | |
Universidad de la República | |
COLIBRI | |
https://hdl.handle.net/20.500.12008/22553 | |
Acceso abierto | |
Licencia Creative Commons Atribución (CC - By 4.0) |
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---|---|
author | Rozenblum, E. |
author2 | Sotelo Silveira, José Roberto Kim, G. Y. Zhu, J. Y. Lau, C. C. McNeil, N. Korolevich, S. Liao, H. Cherry, J. M. Munroe, D. J. Ried, T. Meltzer, P. S. Kuehl, W. M. Roschke, A. V. |
author2_role | author author author author author author author author author author author author author |
author_facet | Rozenblum, E. Sotelo Silveira, José Roberto Kim, G. Y. Zhu, J. Y. Lau, C. C. McNeil, N. Korolevich, S. Liao, H. Cherry, J. M. Munroe, D. J. Ried, T. Meltzer, P. S. Kuehl, W. M. Roschke, A. V. |
author_role | author |
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collection | COLIBRI |
dc.contributor.filiacion.none.fl_str_mv | Rozenblum E. Sotelo Silveira José Roberto, Universidad de la República (Uruguay). Facultad de Ciencias. Instituto de Biología Kim G. Y. Zhu J. Y. Lau C. C. McNeil N. Korolevich S. Liao H. Cherry J. M. Munroe D. J. Ried T. Meltzer P. S. Kuehl W. M. Roschke A. V. |
dc.creator.none.fl_str_mv | Rozenblum, E. Sotelo Silveira, José Roberto Kim, G. Y. Zhu, J. Y. Lau, C. C. McNeil, N. Korolevich, S. Liao, H. Cherry, J. M. Munroe, D. J. Ried, T. Meltzer, P. S. Kuehl, W. M. Roschke, A. V. |
dc.date.accessioned.none.fl_str_mv | 2019-11-26T18:11:28Z |
dc.date.available.none.fl_str_mv | 2019-11-26T18:11:28Z |
dc.date.issued.none.fl_str_mv | 2017 |
dc.description.abstract.none.fl_txt_mv | A new ovarian near-diploid cell line, OVDM1, was derived from a highly aneuploid serous ovarian metastatic adenocarcinoma. A metastatic tumor was obtained from a 47-year-old Ashkenazi Jewish patient three years after the first surgery removed the primary tumor, both ovaries, and the remaining reproductive organs. OVDM1 was characterized by cell morphology, genotyping, tumorigenic assay, mycoplasma testing, spectral karyotyping (SKY), and molecular profiling of the whole genome by aCGH and gene expression microarray. Targeted sequencing of a panel of cancer-related genes was also performed. Hierarchical clustering of gene expression data clearly confirmed the ovarian origin of the cell line. OVDM1 has a near-diploid karyotype with a low-level aneuploidy, but samples of the original metastatic tumor were grossly aneuploid. A number of single nucleotide variations (SNVs)/ mutations were detected in OVDM1 and the metastatic tumor samples. Some of them were cancer-related according to COSMIC and HGMD databases (no founder mutations in BRCA1 and BRCA2 have been found). A large number of focal copy number alterations (FCNAs) were detected, including homozygous deletions (HDs) targeting WWOX and GATA4. Progression of OVDM1 from early to late passages was accompanied by preservation of the near-diploid status, acquisition of only few additional large chromosomal rearrangements and more than 100 new small FCNAs. Most of newly acquired FCNAs seem to be related to localized but massive DNA fragmentation (chromothripsis-like rearrangements). Newly developed near-diploid OVDM1 cell line offers an opportunity to evaluate tumorigenesis pathways/events in a minor clone of metastatic ovarian adenocarcinoma as well as mechanisms of chromothripsis. |
dc.format.extent.es.fl_str_mv | 11 h. |
dc.format.mimetype.es.fl_str_mv | application/pdf |
dc.identifier.citation.es.fl_str_mv | Rozenblum, E., Sotelo, J.R., Kim, G.Y., y otros. "Novel near-diploid ovarian cancer cell line derived from a highly aneuploid metastatic ovarian tumor". PLoS ONE [en línea]. 2017 12 (8), art. no. e0182610. doi: 10.1371/journal.pone.0182610 |
dc.identifier.doi.none.fl_str_mv | 10.1371/journal.pone.0182610 |
dc.identifier.issn.none.fl_str_mv | 1932-6203 |
dc.identifier.uri.none.fl_str_mv | https://hdl.handle.net/20.500.12008/22553 |
dc.language.iso.none.fl_str_mv | en eng |
dc.publisher.es.fl_str_mv | PLoS |
dc.relation.ispartof.es.fl_str_mv | PLoS ONE, 2017 12 (8), art. no. e0182610 |
dc.rights.license.none.fl_str_mv | Licencia Creative Commons Atribución (CC - By 4.0) |
dc.rights.none.fl_str_mv | info:eu-repo/semantics/openAccess |
dc.source.none.fl_str_mv | reponame:COLIBRI instname:Universidad de la República instacron:Universidad de la República |
dc.subject.es.fl_str_mv | Neoplasms Mutation Intratumor heterogeneity |
dc.title.none.fl_str_mv | Novel near-diploid ovarian cancer cell line derived from a highly aneuploid metastatic ovarian tumor |
dc.type.es.fl_str_mv | Artículo |
dc.type.none.fl_str_mv | info:eu-repo/semantics/article |
dc.type.version.none.fl_str_mv | info:eu-repo/semantics/publishedVersion |
description | A new ovarian near-diploid cell line, OVDM1, was derived from a highly aneuploid serous ovarian metastatic adenocarcinoma. A metastatic tumor was obtained from a 47-year-old Ashkenazi Jewish patient three years after the first surgery removed the primary tumor, both ovaries, and the remaining reproductive organs. OVDM1 was characterized by cell morphology, genotyping, tumorigenic assay, mycoplasma testing, spectral karyotyping (SKY), and molecular profiling of the whole genome by aCGH and gene expression microarray. Targeted sequencing of a panel of cancer-related genes was also performed. Hierarchical clustering of gene expression data clearly confirmed the ovarian origin of the cell line. OVDM1 has a near-diploid karyotype with a low-level aneuploidy, but samples of the original metastatic tumor were grossly aneuploid. A number of single nucleotide variations (SNVs)/ mutations were detected in OVDM1 and the metastatic tumor samples. Some of them were cancer-related according to COSMIC and HGMD databases (no founder mutations in BRCA1 and BRCA2 have been found). A large number of focal copy number alterations (FCNAs) were detected, including homozygous deletions (HDs) targeting WWOX and GATA4. Progression of OVDM1 from early to late passages was accompanied by preservation of the near-diploid status, acquisition of only few additional large chromosomal rearrangements and more than 100 new small FCNAs. Most of newly acquired FCNAs seem to be related to localized but massive DNA fragmentation (chromothripsis-like rearrangements). Newly developed near-diploid OVDM1 cell line offers an opportunity to evaluate tumorigenesis pathways/events in a minor clone of metastatic ovarian adenocarcinoma as well as mechanisms of chromothripsis. |
eu_rights_str_mv | openAccess |
format | article |
id | COLIBRI_f36c2a9a6c4dcb4a9df8decece9edbcb |
identifier_str_mv | Rozenblum, E., Sotelo, J.R., Kim, G.Y., y otros. "Novel near-diploid ovarian cancer cell line derived from a highly aneuploid metastatic ovarian tumor". PLoS ONE [en línea]. 2017 12 (8), art. no. e0182610. doi: 10.1371/journal.pone.0182610 1932-6203 10.1371/journal.pone.0182610 |
instacron_str | Universidad de la República |
institution | Universidad de la República |
instname_str | Universidad de la República |
language | eng |
language_invalid_str_mv | en |
network_acronym_str | COLIBRI |
network_name_str | COLIBRI |
oai_identifier_str | oai:colibri.udelar.edu.uy:20.500.12008/22553 |
publishDate | 2017 |
reponame_str | COLIBRI |
repository.mail.fl_str_mv | mabel.seroubian@seciu.edu.uy |
repository.name.fl_str_mv | COLIBRI - Universidad de la República |
repository_id_str | 4771 |
rights_invalid_str_mv | Licencia Creative Commons Atribución (CC - By 4.0) |
spelling | Rozenblum E.Sotelo Silveira José Roberto, Universidad de la República (Uruguay). Facultad de Ciencias. Instituto de BiologíaKim G. Y.Zhu J. Y.Lau C. C.McNeil N.Korolevich S.Liao H.Cherry J. M.Munroe D. J.Ried T.Meltzer P. S.Kuehl W. M.Roschke A. V.2019-11-26T18:11:28Z2019-11-26T18:11:28Z2017Rozenblum, E., Sotelo, J.R., Kim, G.Y., y otros. "Novel near-diploid ovarian cancer cell line derived from a highly aneuploid metastatic ovarian tumor". PLoS ONE [en línea]. 2017 12 (8), art. no. e0182610. doi: 10.1371/journal.pone.0182610 1932-6203https://hdl.handle.net/20.500.12008/2255310.1371/journal.pone.0182610 A new ovarian near-diploid cell line, OVDM1, was derived from a highly aneuploid serous ovarian metastatic adenocarcinoma. A metastatic tumor was obtained from a 47-year-old Ashkenazi Jewish patient three years after the first surgery removed the primary tumor, both ovaries, and the remaining reproductive organs. OVDM1 was characterized by cell morphology, genotyping, tumorigenic assay, mycoplasma testing, spectral karyotyping (SKY), and molecular profiling of the whole genome by aCGH and gene expression microarray. Targeted sequencing of a panel of cancer-related genes was also performed. Hierarchical clustering of gene expression data clearly confirmed the ovarian origin of the cell line. OVDM1 has a near-diploid karyotype with a low-level aneuploidy, but samples of the original metastatic tumor were grossly aneuploid. A number of single nucleotide variations (SNVs)/ mutations were detected in OVDM1 and the metastatic tumor samples. Some of them were cancer-related according to COSMIC and HGMD databases (no founder mutations in BRCA1 and BRCA2 have been found). A large number of focal copy number alterations (FCNAs) were detected, including homozygous deletions (HDs) targeting WWOX and GATA4. Progression of OVDM1 from early to late passages was accompanied by preservation of the near-diploid status, acquisition of only few additional large chromosomal rearrangements and more than 100 new small FCNAs. Most of newly acquired FCNAs seem to be related to localized but massive DNA fragmentation (chromothripsis-like rearrangements). Newly developed near-diploid OVDM1 cell line offers an opportunity to evaluate tumorigenesis pathways/events in a minor clone of metastatic ovarian adenocarcinoma as well as mechanisms of chromothripsis.Submitted by Faget Cecilia (lfaget@fcien.edu.uy) on 2019-11-26T17:45:54Z No. of bitstreams: 2 license_rdf: 19874 bytes, checksum: 38cb62ef53e6f513db2fb7e337df6485 (MD5) 101371journalpone0182610.pdf: 3724416 bytes, checksum: 075410244496966d008934b2792977af (MD5)Approved for entry into archive by Faget Cecilia (lfaget@fcien.edu.uy) on 2019-11-26T17:49:34Z (GMT) No. of bitstreams: 2 license_rdf: 19874 bytes, checksum: 38cb62ef53e6f513db2fb7e337df6485 (MD5) 101371journalpone0182610.pdf: 3724416 bytes, checksum: 075410244496966d008934b2792977af (MD5)Made available in DSpace on 2019-11-26T18:11:28Z (GMT). No. of bitstreams: 2 license_rdf: 19874 bytes, checksum: 38cb62ef53e6f513db2fb7e337df6485 (MD5) 101371journalpone0182610.pdf: 3724416 bytes, checksum: 075410244496966d008934b2792977af (MD5) Previous issue date: 201711 h.application/pdfenengPLoSPLoS ONE, 2017 12 (8), art. no. e0182610Las obras depositadas en el Repositorio se rigen por la Ordenanza de los Derechos de la Propiedad Intelectual de la Universidad de la República.(Res. Nº 91 de C.D.C. de 8/III/1994 – D.O. 7/IV/1994) y por la Ordenanza del Repositorio Abierto de la Universidad de la República (Res. Nº 16 de C.D.C. de 07/10/2014)info:eu-repo/semantics/openAccessLicencia Creative Commons Atribución (CC - By 4.0)NeoplasmsMutationIntratumor heterogeneityNovel near-diploid ovarian cancer cell line derived from a highly aneuploid metastatic ovarian tumorArtículoinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionreponame:COLIBRIinstname:Universidad de la Repúblicainstacron:Universidad de la RepúblicaRozenblum, E.Sotelo Silveira, José RobertoKim, G. Y.Zhu, J. Y.Lau, C. C.McNeil, N.Korolevich, S.Liao, H.Cherry, J. M.Munroe, D. J.Ried, T.Meltzer, P. S.Kuehl, W. M.Roschke, A. 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- Universidad de la Repúblicafalse |
spellingShingle | Novel near-diploid ovarian cancer cell line derived from a highly aneuploid metastatic ovarian tumor Rozenblum, E. Neoplasms Mutation Intratumor heterogeneity |
status_str | publishedVersion |
title | Novel near-diploid ovarian cancer cell line derived from a highly aneuploid metastatic ovarian tumor |
title_full | Novel near-diploid ovarian cancer cell line derived from a highly aneuploid metastatic ovarian tumor |
title_fullStr | Novel near-diploid ovarian cancer cell line derived from a highly aneuploid metastatic ovarian tumor |
title_full_unstemmed | Novel near-diploid ovarian cancer cell line derived from a highly aneuploid metastatic ovarian tumor |
title_short | Novel near-diploid ovarian cancer cell line derived from a highly aneuploid metastatic ovarian tumor |
title_sort | Novel near-diploid ovarian cancer cell line derived from a highly aneuploid metastatic ovarian tumor |
topic | Neoplasms Mutation Intratumor heterogeneity |
url | https://hdl.handle.net/20.500.12008/22553 |