Novel near-diploid ovarian cancer cell line derived from a highly aneuploid metastatic ovarian tumor

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.

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.


Detalles Bibliográficos
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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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.
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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.
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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 
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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