Gross genomic alterations differ between serous borderline tumors and serous adenocarcinomas—an image cytometric DNA ploidy analysis of 307 cases with histogenetic implications

Pradhan, Manohar; Davidson, Ben; Tropé, Claes G.; Danielsen, Håvard E.; Abeler, Vera M.; Risberg, Bjørn

doi:10.1007/s00428-009-0778-y

Cited by 8 publications

(9 citation statements)

References 24 publications

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“…These data are very similar to those described in the whole exome analysis of low grade serous carcinomas [9]. As might be expected, low grade serous invasive carcinomas have a DNA content and level of copy number alterations that more closely resembles SBTs than high grade serous tumors, but which are intermediate between the two [29,30]. In contrast, high grade serous carcinomas are generally aneuploid with a high level of copy number alterations [8,30] and data from the TCGA ovarian study indicate that these tumors typically sustain 50–70 somatic mutations, with TP53 representing a clear driver mutation in this tumor type [8].…”

Section: Resultssupporting

confidence: 86%

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Whole exome sequence analysis of serous borderline tumors of the ovary

Boyd¹,

Luo²,

Peri³

et al. 2013

Gynecologic Oncology

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Objective Serous borderline tumor (SBT) is a unique histopathologic entity of the ovary, believed to be intermediate between benign cystadenoma and invasive low-grade serous carcinoma. While somatic mutations in the KRAS or BRAF, and rarely ERBB2, genes have been well characterized in SBTs, other genetic alterations have not been described. Toward a more comprehensive understanding of the molecular genetic architecture of SBTs, we undertook whole exome sequencing of this tumor type. Methods Following pathologic review and laser capture microdissection to enrich for tumor cells, whole exomes were prepared from DNA of two independent SBTs and subjected to massively parallel DNA sequencing. Results Both tumors contained an activating mutation of the BRAF gene. A total of 15 additional somatic mutations were identified, nine in one tumor and six in the other. Eleven were missense mutations and four were nonsense or deletion mutations. Fourteen of the 16 genes found to be mutated in this study have been reported to be mutated in other cancers. Furthermore, 12 of these genes are mutated in ovarian cancers. The FBXW7 and KIAA1462 genes are noteworthy candidates for a pathogenic role in serous borderline tumorigenesis. Conclusions These findings suggest that a very small number of somatic genetic mutations are characteristic of SBTs of the ovary, thus supporting their classification as a relatively genetically stable tumor type. The mutant genes described herein represent novel candidates for the pathogenesis of ovarian SBT.

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Section: Resultssupporting

confidence: 86%

“…With respect to chromosomal instability, SBTs are relatively genetically stable, in terms of both DNA ploidy [29] and copy number alterations [30], consistent with the low number of genetic mutations identified in this study. Only 10 somatic genetic mutations were identified in tumor SBT-s2, and seven in tumor SBT-s5.…”

Section: Resultssupporting

confidence: 79%

Whole exome sequence analysis of serous borderline tumors of the ovary

Boyd¹,

Luo²,

Peri³

et al. 2013

Gynecologic Oncology

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“…Alternatively, the absence of identifiable KRAS or BRAF mutations in benign serous tumors with clear clonal expansion events leaves open the possibility that they may be precursors for other serous ovarian cancers. The tetrasomy identified in the epithelial component in case A2, adjacent to fibroblasts with chromosome 12 trisomy, is a particularly intriguing finding in light of ploidy studies by Pradhan and colleagues that identified tetraploidy in 7 of 40 high-grade serous carcinomas, 0 of 22 LGSCs, and 0 of 245 SBTs (34).…”

Section: Discussionmentioning

confidence: 82%

Copy Number Aberrations in Benign Serous Ovarian Tumors: A Case for Reclassification?

Hunter

Anglesio

Sharma

et al. 2011

Clinical Cancer Research

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Purpose: Serous ovarian carcinomas are the predominant epithelial ovarian cancer subtype and it has been widely believed that some or all of these may arise from precursors derived from the ovarian surface epithelium or fimbriae, although direct molecular evidence for this is limited. This study aimed to conduct copy number (CN) analysis using a series of benign and borderline serous ovarian tumors to identify underlying genomic changes that may be indicative of early events in tumorigenesis.Experimental Design: High resolution CN analysis was conducted on DNA from the epithelial and fibroblast components of a cohort of benign (N ¼ 39) and borderline (N ¼ 24) serous tumors using the Affymetrix OncoScan assay and SNP6.0 arrays.Results: CN aberrations were detected in the epithelium of only 2.9% (1 of 35) of serous cystadenomas and cystadenofibromas. In contrast, CN aberrations were detected in the epithelium of 67% (16 of 24) of the serous borderline tumors (SBT). Unexpectedly, CN aberrations were detected in the fibroblasts of 33%

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“…These carcinomas have a DNA content and level of copy number alterations that closely resembles that of SBTs [24,25]. …”

Section: Ovarian Carcinoma Typesmentioning

confidence: 99%

Subtypes of Ovarian Cancer and Ovarian Cancer Screening

2017

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Ovarian cancer is the foremost cause of gynecological cancer death in the developed world, as it is usually diagnosed at an advanced stage. In this paper we discuss current issues, the efficacy and problems associated with ovarian cancer screening, and compare the characteristics of ovarian cancer subtypes. There are two types of ovarian cancer: Type I carcinomas, which are slow-growing, indolent neoplasms thought to arise from a precursor lesion, which are relatively common in Asia; and Type II carcinomas, which are clinically aggressive neoplasms that can develop de novo from serous tubal intraepithelial carcinomas (STIC) and/or ovarian surface epithelium and are common in Europe and the USA. One of the most famous studies on the subject reported that annual screening using CA125/transvaginal sonography (TVS) did not reduce the ovarian cancer mortality rate in the USA. In contrast, a recent study in the UK showed an overall average mortality reduction of 20% in the screening group. Another two studies further reported that the screening was associated with decreased stage at detection. Theoretically, annual screening using CA125/TVS could easily detect precursor lesions and could be more effective in Asia than in Europe and the USA. The detection of Type II ovarian carcinoma at an early stage remains an unresolved issue. The resolving power of CA125 or TVS screening alone is unlikely to be successful at resolving STICs. Biomarkers for the early detection of Type II carcinomas such as STICs need to be developed.

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Gross genomic alterations differ between serous borderline tumors and serous adenocarcinomas—an image cytometric DNA ploidy analysis of 307 cases with histogenetic implications

Cited by 8 publications

References 24 publications

Whole exome sequence analysis of serous borderline tumors of the ovary

Whole exome sequence analysis of serous borderline tumors of the ovary

Copy Number Aberrations in Benign Serous Ovarian Tumors: A Case for Reclassification?

Subtypes of Ovarian Cancer and Ovarian Cancer Screening

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