Malignant ovarian germ cell tumours in gonadal Y chromosome mosaicism

Shahsiah, Reza; Jahanbin, Behnaz; Rabiei, Reza; Ardalan, Farid Azmoudeh; Sarhadi, Behnaz; Izadi-Mood, Narges

doi:10.1136/jcp.2011.090738

Cited by 11 publications

(6 citation statements)

References 21 publications

(22 reference statements)

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“…been restricted to tumors that show gonadoblastoma histology ( • ▶ Table 3 ), so that genetic analysis is more sensitive than histologic screen for gonadoblastoma. Compared to our cohort, unilateral oGCTs show Y-chromosomal material less frequently, e. g. 7 out of 47 patients being positive for TSPY in a recent study [ 23 ] . This indicates the importance of Y-chromosomal genes in the development of bilateral oGCTs.…”

contrasting

confidence: 83%

“…There are data suggesting, that bilateral oGCTs may be associated either with gonadal dysgenesis or c-kit mutation [ 9 ] . In this context, our study provides important information, in spite of the small study cohort [ 23 ] . In this exquisite series of patients with clinically insuspicious females with bilateral oGCTs, Y-chromosomal DNA was detected in approximately half of patients.…”

Section: Polymerase Chain Reaction (Pcr)mentioning

confidence: 89%

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Molecular Genetic Analysis of Bilateral Ovarian Germ Cell Tumors

et al. 2012

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These investigations provide additional insight into the development of oGCTs: mature teratomas, which develop from postmeiotic germ cells, are not associated with gonadal dysgenesis. Bilateral immature teratomas, dysgerminomas and mixed malignant oGCTs may frequently show Y-chromosomal DNA, indicating underlying but clinically inapparent gonadal dysgenesis. Thus, the presence of aberrant Y-chromosomal sequences appears to be involved in tumor development in about half of these patients.

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contrasting

confidence: 83%

Section: Polymerase Chain Reaction (Pcr)mentioning

confidence: 89%

Molecular Genetic Analysis of Bilateral Ovarian Germ Cell Tumors

et al. 2012

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“…Presence of the TSPY gene in malignant ovarian germ cell tumors has also been studied by Shahsiah et al . [41], showing positivity of the gene in 6 out of 47 (12.7%) cases, two patients showed GB and in one patient presence of the Y chromosome was confirmed cytogenetically. However, no c-KIT mutation analysis was performed.…”

Section: Discussionmentioning

confidence: 84%

Prevalence of c-KIT Mutations in Gonadoblastoma and Dysgerminomas of Patients with Disorders of Sex Development (DSD) and Ovarian Dysgerminomas

et al. 2012

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Activating c-KIT mutations (exons 11 and 17) are found in 10–40% of testicular seminomas, the majority being missense point mutations (codon 816). Malignant ovarian dysgerminomas represent ∼3% of all ovarian cancers in Western countries, resembling testicular seminomas, regarding chromosomal aberrations and c-KIT mutations. DSD patients with specific Y-sequences have an increased risk for Type II Germ Cell Tumor/Cancer, with gonadoblastoma as precursor progressing to dysgerminoma. Here we present analysis of c-KIT exon 8, 9, 11, 13 and 17, and PDGFRA exon 12, 14 and 18 by conventional sequencing together with mutational analysis of c-KIT codon 816 by a sensitive and specific LightCycler melting curve analysis, confirmed by sequencing. The results are combined with data on TSPY and OCT3/4 expression in a series of 16 DSD patients presenting with gonadoblastoma and dysgerminoma and 15 patients presenting pure ovarian dysgerminomas without DSD. c-KIT codon 816 mutations were detected in five out of the total of 31 cases (all found in pure ovarian dysgerminomas). A synonymous SNP (rs 5578615) was detected in two patients, one DSD patient (with bilateral disease) and one patient with dysgerminoma. Next to these, three codon N822K mutations were detected in the group of 15 pure ovarian dysgerminomas. In total activating c-KIT mutations were found in 53% of ovarian dysgerminomas without DSD. In the group of 16 DSD cases a N505I and D820E mutation was found in a single tumor of a patient with gonadoblastoma and dysgerminoma. No PDGFRA mutations were found. Positive OCT3/4 staining was present in all gonadoblastomas and dysgerminomas investigated, TSPY expression was only seen in the gonadoblastoma/dysgerminoma lesions of the 16 DSD patients. This data supports the existence of two distinct but parallel pathways in the development of dysgerminoma, in which mutational status of c-KIT might parallel the presence of TSPY.

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“…The number of mOGCTs with documented gene mutations remains low, and most mOGCTs in DSD patients include the presence of some Y-chromosome material (59). mOGCTs may also develop against a background of gonadal Y-chromosome mosaicism (128). This also leads to a diagnostic problem for identification of patients with increased risk for bilateral disease.…”

Section: Introductionmentioning

confidence: 99%

Molecular Characteristics of Malignant Ovarian Germ Cell Tumors and Comparison With Testicular Counterparts: Implications for Pathogenesis

et al. 2013

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This review focuses on the molecular characteristics and development of rare malignant ovarian germ cell tumors (mOGCTs). We provide an overview of the genomic aberrations assessed by ploidy, cytogenetic banding, and comparative genomic hybridization. We summarize and discuss the transcriptome profiles of mRNA and microRNA (miRNA), and biomarkers (DNA methylation, gene mutation, individual protein expression) for each mOGCT histological subtype. Parallels between the origin of mOGCT and their male counterpart testicular GCT (TGCT) are discussed from the perspective of germ cell development, endocrinological influences, and pathogenesis, as is the GCT origin in patients with disorders of sex development. Integrated molecular profiles of the 3 main histological subtypes, dysgerminoma (DG), yolk sac tumor (YST), and immature teratoma (IT), are presented. DGs show genomic aberrations comparable to TGCT. In contrast, the genome profiles of YST and IT are different both from each other and from DG/TGCT. Differences between DG and YST are underlined by their miRNA/mRNA expression patterns, suggesting preferential involvement of the WNT/β-catenin and TGF-β/bone morphogenetic protein signaling pathways among YSTs. Characteristic protein expression patterns are observed in DG, YST and IT. We propose that mOGCT develop through different developmental pathways, including one that is likely shared with TGCT and involves insufficient sexual differentiation of the germ cell niche. The molecular features of the mOGCTs underline their similarity to pluripotent precursor cells (primordial germ cells, PGCs) and other stem cells. This similarity combined with the process of ovary development, explain why mOGCTs present so early in life, and with greater histological complexity, than most somatic solid tumors.

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Malignant ovarian germ cell tumours in gonadal Y chromosome mosaicism

Cited by 11 publications

References 21 publications

Molecular Genetic Analysis of Bilateral Ovarian Germ Cell Tumors

Molecular Genetic Analysis of Bilateral Ovarian Germ Cell Tumors

Prevalence of c-KIT Mutations in Gonadoblastoma and Dysgerminomas of Patients with Disorders of Sex Development (DSD) and Ovarian Dysgerminomas

Molecular Characteristics of Malignant Ovarian Germ Cell Tumors and Comparison With Testicular Counterparts: Implications for Pathogenesis

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