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

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 reprod...

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Main Authors: Ester Rozenblum, Jose R Sotelo-Silveira, Gina Y Kim, Jack Y Zhu, Christopher C Lau, Nicole McNeil, Susana Korolevich, Hongling Liao, James M Cherry, David J Munroe, Thomas Ried, Paul S Meltzer, Walter M Kuehl, Anna V Roschke
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2017-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0182610&type=printable
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author Ester Rozenblum
Jose R Sotelo-Silveira
Gina Y Kim
Jack Y Zhu
Christopher C Lau
Nicole McNeil
Susana Korolevich
Hongling Liao
James M Cherry
David J Munroe
Thomas Ried
Paul S Meltzer
Walter M Kuehl
Anna V Roschke
author_facet Ester Rozenblum
Jose R Sotelo-Silveira
Gina Y Kim
Jack Y Zhu
Christopher C Lau
Nicole McNeil
Susana Korolevich
Hongling Liao
James M Cherry
David J Munroe
Thomas Ried
Paul S Meltzer
Walter M Kuehl
Anna V Roschke
author_sort Ester Rozenblum
collection DOAJ
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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spelling doaj-art-dba79d739dea4b88b3e99d1b86610c4c2025-08-20T02:46:01ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01128e018261010.1371/journal.pone.0182610Novel near-diploid ovarian cancer cell line derived from a highly aneuploid metastatic ovarian tumor.Ester RozenblumJose R Sotelo-SilveiraGina Y KimJack Y ZhuChristopher C LauNicole McNeilSusana KorolevichHongling LiaoJames M CherryDavid J MunroeThomas RiedPaul S MeltzerWalter M KuehlAnna V RoschkeA 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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0182610&type=printable
spellingShingle Ester Rozenblum
Jose R Sotelo-Silveira
Gina Y Kim
Jack Y Zhu
Christopher C Lau
Nicole McNeil
Susana Korolevich
Hongling Liao
James M Cherry
David J Munroe
Thomas Ried
Paul S Meltzer
Walter M Kuehl
Anna V Roschke
Novel near-diploid ovarian cancer cell line derived from a highly aneuploid metastatic ovarian tumor.
PLoS ONE
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
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0182610&type=printable
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