Elsevier

Human Pathology

Volume 52, June 2016, Pages 128-135
Human Pathology

Original contribution
Genetic analysis results of mature cystic teratomas of the ovary in Taiwan disagree with the previous origin theory of this tumor,☆☆

https://doi.org/10.1016/j.humpath.2016.01.011Get rights and content

Summary

The most accepted theory regarding mature cystic teratomas of the ovary is that they are of parthenogenetic origin from oocyte after the completion of first division. Our previous study demonstrated that the origin of mature cystic teratoma of the uterus is not related to the parthenogenetic process, but is most likely pluripotential stem cell or primordial germ cell before meiosis I. Further studies are needed to clarify the origin of benign mature cystic teratomas of the ovary in Taiwan. In the present study, we investigated the DNA profiles of 9 mature cystic teratomas of the ovary using short tandem repeat analysis with AmpFLSTR SGM Plus, Profiler PCR amplification kits. The methylation statuses of the HhaI sites in the SNRPN, H19DMR, and KvDMR regions were determined on methylation-sensitive multiplex ligation-dependent probe amplification analysis. DNA profiling data from the 9 mature cystic teratomas of the ovary excluded parthenogenetic origin, as most of the 15 short tandem repeat loci were heterozygous on genotyping. There were varying degrees of hypermethylation of SNRPN gene and KvDMR locus in the presence of maternal uniparental disomy in all 9 mature cystic teratomas of the ovary. In light of these results, we further postulated that the origin of these mature cystic teratomas of the ovary is oogonia or primary oocyte before germinal vesicle stage failure of meiosis I.

Introduction

Teratomas are common germ cell tumors [1]. They are defined histologically as containing tissues derived from all 3 germ cell layers: ectoderm, mesoderm, and endoderm [1]. Extragonadal germ cell tumors represent only 1% to 5% of all germ cell tumors and frequently present as sacrococcygeal teratomas [2]. Other extragonadal sites include the mediastinum, head and neck region, and retroperitoneum [2]. Teratomas are also classified as mature or immature, depending on the degree of differentiation of their components [1]. The most common locations are the ovaries, although they may also occur in the testes [3]. Other sites include midline structure of germline cell migration. Ovarian teratomas include mature cystic teratomas (dermoid cysts), immature teratomas, and monodermal teratomas (eg, struma ovarii, carcinoid tumors, and neural tumors) [1]. In ovaries, most benign teratomas are cystic. Thus, they are often referred to in clinical parlance as dermoid cysts [3]. Mature cystic teratomas can contain several different tissue types, including skin, hair, muscle, and bone, and are usually found in young women during their active reproductive years [3]. They may be discovered incidentally but are occasionally associated with clinically important paraneoplastic syndromes, such as inflammatory limbic encephalitis, which may remit upon removal of the tumor [3]. Benign mature cystic teratomas of the ovary are bilateral in 10% to 15% of cases [3].

There exist a number of theories on the origin of benign mature cystic teratomas of the ovary: failure of meiosis I or fusion of the first polar body with the oocyte, failure of meiosis II of the second polar body with the ootid, duplication of the genome of a mature ovum, failure of meiosis I and II in the primordial germ cell, and fusion of 2 ova [4]. The most accepted theory is parthenogenetic origin. Parthenogenesis refers to embryonic development without the male gamete. In 1970, Linder and Power [5] proposed that benign mature cystic teratomas of the ovary are induced by parthenogenetically activated ovarian oocytes that have completed the first meiotic division. Chromosome-banding studies performed by Linder et al [6] showed tumor tissues homozygous for 17 chromosome polymorphisms at or near the centromere, indicating that benign mature cystic teratomas of the ovary are parthenogenetic tumors that arise from a single germ cell after the first meiotic division. In addition, teratomas have been produced by grafting early embryos onto various sites in adult mice [7]. In a minority of cases, mature cystic teratomas of the ovary have been found to originate from germ cell failure of meiosis I [8], [9]. Vortmeyer et al [10] conducted tissue microdissection followed by genetic analysis of mature cystic teratomas of the ovary, and their results strongly support Linder's original hypothesis of a germ cell origin.

Chromosome banding studies and enzyme polymorphisms were used to investigate the pathogenesis of gonadal teratomas from the 1970s to the 1990s [4], [5], [6], [7], [8], [9]. Later, tissue microdissection followed by genetic analysis of microsatellite polymorphic markers was applied to identify allelic losses [10]. It is now thought that benign mature cystic teratomas of the ovary can originate at any stage of female gametogenesis [11].

Our previous study using AmpFLSTR SGM Plus and AmpFLSTR Profiler PCR amplification kits (Applied Biosystems, Taipei, Taiwan) showed that the origin of mature cystic teratoma of the uterus is most likely pluripotential stem cell of uterus or primordial germ cell before meiosis I [12]. In that study, several loci, such as FGA, D21S11, and D19S433, showed significant loss of heterozygosity (LOH), mostly likely the result of tumor formation or the participation of their products in the development of mature cystic teratomas of the uterus [12]. Further studies are needed to better understand the origin of benign mature cystic teratomas of the ovary in Taiwan. In the present study, we analyzed the DNA profiles and methylation statuses of 9 benign mature cystic teratomas of the ovary in an attempt to clarify the origin of this tumor.

Section snippets

Clinical samples

The institutional review board of Jen-Ai Hospital approved all procedures, and informed consent was obtained from all patients prior to collecting their genetic material for the study. Nine 20- to 40-year-old patients with mature cystic teratoma of the ovary were enrolled. They sought medical attention and were operated on between January 1, 2013, and December 31, 2014. Their cystic masses contained fat, hair, and bony tissue. Teratoma samples (Tera-1 to Tera-9) were obtained from the innermost

Genotypes of 15 STR loci

The genotype results of 15 STR loci are presented in Table 2. Eight of the 15 analyzed STRs in Tera-1 were heterozygous. The remaining 7 were homozygous: D2S1338, D5S818, D7S820, TH01, D13S317, D16S539, and D18S51. Eight of the 15 STRs in Tera-2 were heterozygous (Table 2). The remaining 7 were homozygous: D2S1338, D3S1358, FGA, D7S820, vWA, D19S433, and D21S11. There were 3 STR loci in Tera-3 (Table 2 and Fig. 1) with 3 alleles: D7S820, TH01, and D19S433. Nine of the 15 STRs in Tera-3 were

Discussion

Human ovarian tumors originate from oocytes at all meiotic stages. Most develop from oocytes that have completed meiosis I by virgin birth or parthenogenesis [4], [8], [13]. Our previous study demonstrated that mature cystic teratoma of the uterus does not originate from the parthenogenetic process [12]. In this study, the heterozygosity in our DNA profiling data did not support a parthenogenetic origin of mature cystic teratomas of the ovary (Table 2 and Fig. 1), which is consistent with a

Supplementary data

The following are the supplementary data related to this article.

. Electropherogram of the DNA profiles of Tera-5N (A and B) and Tera-5 (C and D). A and C, STR loci of D8S1179, D21S11, D7S820, and CSF1PO. B and D, STR loci of D3S1358, TH01, D13S317, D16S539, and D2S1338.

. The orders of percentage of methylation in the 15q11 SNRPN, 11p15 KvDMR, and H19DMR probes in teratomas

Acknowledgments

The authors would like to thank GenePhile Bioscience Laboratory of Ko's Obstetrics and Gynecology Clinic for help with acquisition of data.

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    Competing Interest: None.

    ☆☆

    Funding/Support: Research Grant 10408-1 from Jen-Ai Hospital, Taichung, Taiwan.

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