Genetic alterations of serous borderline tumors of the ovary compared to stage I serous ovarian carcinomas

Österberg, Lovisa; Åkeson, Margaretha; Levan, Kristina; Partheen, Karolina; Zetterqvist, Britt-Marie; Brännström, Mats; Horváth, György

doi:10.1016/j.cancergencyto.2006.01.009

Cited by 18 publications

(15 citation statements)

References 28 publications

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“…Gain in chromosome arm 8q was highly associated with serous and clear cell subtypes. This relationship outcome is in agreement with our previous metaphase CGH results where gain in 8q was found associated with serous and clear cell tumours [Osterberg et al, 2005] and was also found to be an early event in serous ovarian carcinogenesis [Osterberg et al, 2006]. Using array CGH, we confirmed the results and specified one SRO to 8q24.22-q24.23.…”

Section: Discussionsupporting

confidence: 81%

“…Several genes are located in 8q24, including the well-known oncogene MYC . In our previous studies, we found loss in 17q to be characteristic of the serous subtype in ovarian tumours [Osterberg et al, 2005[Osterberg et al, , 2006. Here, we confirm these findings and narrow down the region of interest to 17q11.2-q12.…”

Section: Discussionsupporting

confidence: 75%

“…This difference has been observed in previous studies and is an interesting phenomenon [Sonoda et al, 1997;Tapper et al, 1997;Mayr et al, 2006;Osterberg et al, 2006]. Correspondingly, 5-year survival of patients with serous carcinoma is lower (41%) compared to mucinous and clear cell tumours (65.4 and 63.6%, respectively) [Heintz et al, 2006].…”

Section: Discussionmentioning

confidence: 65%

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High-Resolution Genomic Profiling of Carboplatin Resistance in Early-Stage Epithelial Ovarian Carcinoma

Österberg

Levan²,

Partheen³

et al. 2009

Cytogenet Genome Res

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Chemotherapy resistance remains a major obstacle to successful treatment of ovarian cancer patients. Therefore, increased knowledge of underlying mechanisms and identification of predictive factors are of great importance. Standard treatment for ovarian carcinoma is surgery followed by platinum-based chemotherapy. In this study, we aimed to search for genes or genomic regions involved in platinum resistance in ovarian carcinoma. Array-based comparative genomic hybridization (CGH) was used to identify genetic alterations in 32 early-stage epithelial ovarian carcinomas homogeneously treated with single-agent carboplatin. The arrays contain 33,370 bacterial artificial chromosome (BAC) clones and form a contiguous and tiling coverage of the human genome with an average resolution of ∼100 kb. We found certain genetic changes associated with carboplatin response. Gains in 1q25.1–q41 were significantly more frequent in carboplatin-resistant tumours. In this region, we further detected two smallest regions of overlap (SRO) at 1q25.2 and 1q32.2 (∼690 and ∼830 kb in size, respectively). Interestingly, we found some regions that were lost exclusively in the sensitive tumours 17q24.1, Xq21.33–q22.1, and 6 regions in 15q. We also detected genetic differences with regard to histologic subtype. Gain in 8q was found highly associated with serous and clear cell subtypes, and an SRO was identified at 8q24.22–q24.23. The genomic regions found altered in this study confirm some of our previous metaphase CGH results. The alteration found in chromosome arm 1q was verified and specified, and is therefore of great interest as a candidate for predictive markers. Identifying predictive markers of chemosensitive and chemoresistant disease would greatly help in the choice of chemotherapy in the clinic, and thus improve treatment of women with ovarian cancer.

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Section: Discussionsupporting

confidence: 81%

Section: Discussionsupporting

confidence: 75%

Section: Discussionmentioning

confidence: 65%

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High-Resolution Genomic Profiling of Carboplatin Resistance in Early-Stage Epithelial Ovarian Carcinoma

Österberg

Levan²,

Partheen³

et al. 2009

Cytogenet Genome Res

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“…In an alternate pathway, high-grade serous tumours arise without a recognizable precursor or intermediate lesion (63). Comparative genomic hybridization analyses have identified chromosome 17 loss in both LMP and stage I invasive tumours, suggesting chromosome 17 loss to be an early event in the development of serous ovarian cancers or characterizes those LMP tumours that are likely to become invasive (64). Noteworthy, of the 11 LMP tumour samples investigated in our initial LOH analysis of chromosome 17 (21), only one sample exhibited LOH and this sample exhibited loss of the 17q25.1 region.…”

Section: Discussionmentioning

confidence: 88%

Chromosome 17q25 genes, RHBDF2 and CYGB, in ovarian cancer

et al. 2012

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Abstract. It has been proposed that the frequent loss of heterozygosity (LOH) of an entire chromosome 17 contig in epithelial ovarian cancers (EOC) is the consequence of the inactivation of multiple tumour suppressor genes on this chromosome. We report the characterization of a 453 Kb 17q25 locus shown previously to exhibit a high frequency of LOH in EOC samples. LOH analysis further defined the minimal region of deletion to a 65 Kb interval flanked by D17S2239 and D17S2244, which contains RHBDF2, CYGB and PRCD as tumour suppressor gene candidates. Tissue specific expression excluded PRCD as a candidate. RHBDF2 was expressed at low levels in the majority of benign and low malignant potential (LMP) tumours, and in a subset of malignant ovarian tumour samples, as compared with primary cultures of normal ovarian surface epithelial cell (NOSE) samples. CYGB was expressed at low levels in the majority of LMP and malignant samples compared with benign and NOSE samples. In contrast to CYGB expression, RHBDF2 was expressed at low or undetectable levels in EOC cell lines exhibiting tumourigenic characteristics and up-regulated in a genetically modified EOC cell line rendered non-tumourigenic. DNA sequence analysis identified variants but no apparent deleterious mutations in either gene. Methylation-specific PCR analysis suggested that promoter methylation of CYGB but not RHBDF2 occurred in 6 of 31 malignant samples. The results combined suggest that RHBDF2 and CYGB may play distinctive roles in ovarian cancer and could be added to the growing roster of chromosome 17 genes implicated in this disease.

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“…Genetic alteration affects the functioning of many kinds of cells and/or tissues [3,4]. However, little is known about the genetic alterations that may be involved in FCO.…”

Section: Introductionmentioning

confidence: 99%

Identification of Differentially Expressed Genes in Bovine Follicular Cystic Ovaries

Choe

Cho

Kim

et al. 2010

Korean J Physiol Pharmacol

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Follicular cystic ovary (FCO) is one of the most frequently diagnosed ovarian diseases and is a major cause of reproductive failure in mammalian species. However, the mechanism by which FCO is induced remains unclear. Genetic alterations which affect the functioning of many kinds of cells and/or tissues could be present in cystic ovaries. In this study, we performed a comparison analysis of gene expression in order to identify new molecules useful in discrimination of bovine FCO with follicular cystic follicles (FCFs). Normal follicles and FCFs were classified based on their sizes (5 to 10 mm and ≥25 mm). These follicles had granulosa cell layer and theca interna and the hormone 17β-estradiol (E2)/ progesterone (P4) ratio in follicles was greater than one. Perifollicular regions including follicles were used for the preparation of RNA or protein. Differentially expressed genes (DEG) that showed greater than a 2-fold change in expression were screened by the annealing control primer (ACP)-based PCR method using GeneFishing TM DEG kits in bovine normal follicles and FCFs. We identified two DEGs in the FCFs: ribosomal protein L15 (RPL15) and microtubule-associated protein 1B (MAP1B) based on BLAST searches of the NCBI GenBank. Consistent with the ACP analysis, semi-quantitative PCR data and Western blot analyses revealed an up-regulation of RPL15 and a down-regulation of MAP1B in FCFs. These results suggest that RPL15 and MAP1B may be involved in the regulation of pathological processes in bovine FCOs and may help to establish a bovine gene data-base for the discrimination of FCOs from normal ovaries.

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Genetic alterations of serous borderline tumors of the ovary compared to stage I serous ovarian carcinomas

Cited by 18 publications

References 28 publications

High-Resolution Genomic Profiling of Carboplatin Resistance in Early-Stage Epithelial Ovarian Carcinoma

High-Resolution Genomic Profiling of Carboplatin Resistance in Early-Stage Epithelial Ovarian Carcinoma

Chromosome 17q25 genes, RHBDF2 and CYGB, in ovarian cancer

Identification of Differentially Expressed Genes in Bovine Follicular Cystic Ovaries

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