Development Of Gonadoblastoma Research Articles

Bilateral Gonadoblastoma in a 13-Year-Old Female with Turner Syndrome and Y Chromosome: A Case Report

Abstract Introduction/Objective Gonadoblastoma is a relatively rare type of ovarian tumor that has a high risk for patients with 45X/46XY. It is derived from the Y chromosome at its long arm GBY region, which contains the most likely candidate gene called testis-specific protein Y-encoded (TSPY). Methods/Case Report In this case report, we present a case of a 13-year-old girl with Turner syndrome whose cytogenetic test showed 45X with monosomy X and a siodicentric Yq chromosome. As she carried a high risk for the development of gonadoblastoma due to the presence of the Y chromosome and clinically had premature ovarian failure, she received further imaging studies, which did not reveal obvious ovarian masses. She underwent resections of bilateral fallopian tubes and ovaries. Bilateral fallopian tubes were unremarkable. However, within the bilateral ovarian tissue, foci of gonadoblastoma were found (0.5 to 0.6 cm), composed of large round germ cells (confirmed by positive OCT 3/4 and SALL4 stains) intermingled with oval-shaped sex cord-stromal cells forming tubular/cribriform structures (confirmed by positive staining for inhibin, calretinin, and FOXL2). The stromal cells of gonadoblastoma, but not germ cells, were positive for androgen receptor staining, while both components were negative for estrogen receptor staining. No invasive germ cell tumor or sex cord tumor was present. Results (if a Case Study enter NA) N/A Conclusion The positive androgen receptor staining in stromal cells of the gonadoblastoma supports the view that the Y chromosome-driven androgen system may play a role in the development of gonadoblastoma in a bi-cellular pattern.

Seminoma in 46, XY Gonadal Dysgenesis: Rare Presentation and Review of the Literature.

Swyer syndrome is a rare congenital condition that serves as a risk factor for developing germ cell tumors. The condition belongs to the group of 46, XY Disorders of Sexual Development (DSD) is characterized by complete gonadal dysgenesis and is mostly manifested as delayed puberty and primary amenorrhea during adolescence. Individuals with Swyer syndrome are known to be phenotypically female with normal internal and external female genitalia at birth. 46, XY gonadal dysgenesis involves a high risk of gonadoblastoma development with malignant potential such that the onset is greatest at or after the event of puberty. This report of a 12-year-old phenotypic female with 46, XY gonadal dysgenesis, who developed an advanced metastatic seminoma, aims to emphasize the rarity of the development of a seminoma in the context of 46, XY CGD.

Y Chromosome Material in Turner Syndrome.

BackgroundTurner Syndrome (TS) is a frequently identified chromosomal disease in humans characterized by short stature, sexual infantilism, streak gonads, primary amenorrhea, and a number of somatic anomalies. Approximately 55% of TS individuals have a nonmosaic 45,X karyotype. In addition, a cell line with a Y chromosome is present in 5% of patients, which is undetectable by the standard cytogenetic analysis. The identification of Y chromatin in some TS individuals has been associated with the development of gonadoblastoma. Therefore, it is important to exclude the presence of Y chromatin in TS individuals. In this study, it was planned to detect cases with mosaicism in terms of Y chromatin with the help of Y whole chromosome probes (WCP) from individuals with TS by fluorescence in situ hybridization (FISH) analysis.MethodologyForty-four patients with Turner syndrome, who were being followed up in the Genetics Unit, were contacted and invited for the study. Of the 44 invited patients, 28 responded to the invitation. In this study, it was planned to detect TS patients with mosaicism in terms of Y chromatin with the help of the Y whole chromosome probe.ResultsThe majority of the cases (71.42%) included in the study carried pure X monosomy, which is the classical Turner syndrome karyotype. Other structural X chromosome aberrations, in isolated or mosaic forms, were less frequently represented. Y chromosome sequences were searched in 28 cases with Turner syndrome by the FISH method using Y whole chromosome probe. Y chromosome sequence was detected in one (3.5%) case of 28 cases.ConclusionsIt is recommended that individuals with Turner syndrome be screened for Y chromatin. Detection of this will provide information and guidance to individuals with Turner syndrome, especially in terms of the risk of developing gonadoblastoma, with advanced clinical consultation. This study was conducted to emphasize the importance of this.

Recognition of the Y chromosome in Turner syndrome using peripheral blood or oral mucosa tissue.

PurposeTurner syndrome is defined as total or partial loss of the second sex chromosome in a phenotypically female patient. Due to the possibility of hidden mosaicism of fragments of the Y chromosome and development of gonadoblastoma, we evaluated the presence of such fragments in 2 tissues with different embryonic origins, peripheral blood lymphocytes (mesoderm), and oral mucosal cells (ectoderm) using multiplex polymerase chain reaction.MethodsDNA samples were collected from 109 patients, and primers for the SRY, TSPY, and AMELX genes were used.ResultsWe found 14 patients (12.8%) with positive molecular markers for the Y chromosome. The study of tissues of different embryological origin showed the same degree of agreement, sensitivity, and specificity.ConclusionsOral mucosa cells have a simpler method of collection that is less invasive and requires less time for DNA extraction at a lower cost.

Gonadoblastoma in Turner Syndrome: A Surprise in a Streak

Turner syndrome (TS) is a difference in sex development (DSD) affecting 25-50 per 100,000 females with many cardiac, endocrine, neurocognitive, genitourinary, and reproductive implications.1 There is a spectrum of TS depending on degree of chromosomal mosaicism, with particular interest given to those with Y chromosome material present (∼5.5% of TS), which may increase the risk of gonadal malignancy.2 In particular, the expression of testis-specific protein-Y gene is implicated in development of gonadoblastoma (Gb), a premalignant condition found in some patients with DSD.

Risk of Gonadoblastoma Development in Patients with Turner Syndrome with Cryptic Y Chromosome Material.

Current guidelines recommend that testing for Y chromosome material should be performed only in patients with Turner syndrome harboring a marker chromosome and exhibiting virilization in order to detect individuals who are at high risk of gonadoblastoma. However, cryptic Y chromosome material is suggested to be a risk factor for gonadoblastoma in patients with Turner syndrome. Here, we aimed to estimate the frequency of cryptic Y chromosome material in patients with Turner syndrome and determine whether Y chromosome material increased the risk for development of gonadoblastoma. A total of 124 patients who were diagnosed with Turner syndrome by conventional cytogenetic techniques underwent additional molecular analysis to detect cryptic Y chromosome material. In addition, patients with Turner syndrome harboring Y chromosome cell lines had their ovaries removed prophylactically. Finally, we assessed the occurrence of gonadoblastoma in patients with Turner syndrome. Molecular analysis demonstrated that 10 patients had Y chromosome material among 118 patients without overt Y chromosome (8.5%). Six patients with overt Y chromosome and four patients with cryptic Y chromosome material underwent oophorectomy. Histopathological analysis revealed that the occurrence of gonadoblastoma in the total group was 2.4%, and gonadoblastoma occurred in one of six patients with an overt Y chromosome (16.7%) and 2 of 10 patients with cryptic Y chromosome material (20.0%). The risk of developing gonadoblastoma in patients with cryptic Y chromosome material was similar to that in patients with overt Y chromosome. Therefore, molecular screening for Y chromosome material should be recommended for all patients with Turner syndrome to detect individuals at a high risk of gonadoblastoma and to facilitate proper management of the disease.

45,X mosaicism with Y chromosome presenting female phenotype

Prophylactic gonadectomy is recommended in patients with 45,X mosaicism with the Y chromosome and presenting a female phenotype because of the risk of gonadoblastoma development. The characteristics of this disorder remain unclear because of its low incidence. We report 4 patients with 45,X mosaicism with the Y chromosome and presenting complete female external genitalia. We analyzed the characteristics and the macroscopic and histopathological findings of their gonads and performed hormonal assays of the 4 patients. All 4 patients were referred to us with short stature as the chief complaint. Chromosomal studies revealed 45,X/47,XYY in 1, and the others had a 45,X/46,XY karyotype. Three patients (6 gonads) underwent laparoscopic bilateral gonadectomy. The macroscopic appearance of gonads of 1 patient was similar to an ovary, whereas gonads of the rest appeared as streak gonads. The histopathological findings revealed bilateral gonadoblastoma in 1 patient, although the macroscopic findings did not show tumor characteristics. It is impossible to distinguish the histopathological findings of gonads according to their macroscopic appearance among patients with 45,X mosaicism with the Y chromosome and presenting a female phenotype.

Gonadoblastoma in Patients with Ullrich-Turner Syndrome

Ullrich-Turner syndrome (UTS) is a common chromosomal abnormality caused by partial or complete X chromosome monosomy. One half of the patients have a 45,X karyotype, whereas the remaining patients display other X chromosome anomalies. In 6% to 11% of UTS, a normal or partly deleted Y chromosome has been found. A 10% to 30% risk of developing gonadoblastoma was found in the latter patients. The aim of this study was to evaluate the prevalence of Y chromosome-derived material, the occurrence of gonadoblastoma, and the incidence of possible neoplasms in patients with UTS. Of 217 patients studied with UTS and chromosome analysis of peripheral-blood lymphocytes, Y chromosome material was found in 20 patients. Fluorescence in situ hybridization (FISH) testing was performed to characterize the structurally abnormal Y chromosome in 13 cases. Molecular analysis of the SRY gene could only be performed in 20 patients with 45,X karyotype. Two patients had the SRY genomes. Of the 20 patients with Y chromosome-derived material, 17 underwent gonadectomy. The incidence of gonadoblastoma development in our series was 35.5%. Furthermore, 1 patient also showed a pure dysgerminoma, and another showed a mixed dysgerminoma and embryonal carcinoma. We emphasize the importance of complete processing of the gonadectomy specimen, including step sections, molecular studies, and FISH, in addition to the classic cytogenetic searching for Y chromosome sequences, in patients who present with a nonmosaic 45,X karyotype. Finally, we propose to routinely collect a sample for storage in the tumor bank for future studies.

Pathway-based analysis of GWAs data identifies association of sex determination genes with susceptibility to testicular germ cell tumors.

Genome-wide association (GWA) studies of testicular germ cell tumor (TGCT) have identified 18 susceptibility loci, some containing genes encoding proteins important in male germ cell development. Deletions of one of these genes, DMRT1, lead to male-to-female sex reversal and are associated with development of gonadoblastoma. To further explore genetic association with TGCT, we undertook a pathway-based analysis of SNP marker associations in the Penn GWAs (349 TGCT cases and 919 controls). We analyzed a custom-built sex determination gene set consisting of 32 genes using three different methods of pathway-based analysis. The sex determination gene set ranked highly compared with canonical gene sets, and it was associated with TGCT (FDRG = 2.28 × 10(-5), FDRM = 0.014 and FDRI = 0.008 for Gene Set Analysis-SNP (GSA-SNP), Meta-Analysis Gene Set Enrichment of Variant Associations (MAGENTA) and Improved Gene Set Enrichment Analysis for Genome-wide Association Study (i-GSEA4GWAS) analysis, respectively). The association remained after removal of DMRT1 from the gene set (FDRG = 0.0002, FDRM = 0.055 and FDRI = 0.009). Using data from the NCI GWA scan (582 TGCT cases and 1056 controls) and UK scan (986 TGCT cases and 4946 controls), we replicated these findings (NCI: FDRG = 0.006, FDRM = 0.014, FDRI = 0.033, and UK: FDRG = 1.04 × 10(-6), FDRM = 0.016, FDRI = 0.025). After removal of DMRT1 from the gene set, the sex determination gene set remains associated with TGCT in the NCI (FDRG = 0.039, FDRM = 0.050 and FDRI = 0.055) and UK scans (FDRG = 3.00 × 10(-5), FDRM = 0.056 and FDRI = 0.044). With the exception of DMRT1, genes in the sex determination gene set have not previously been identified as TGCT susceptibility loci in these GWA scans, demonstrating the complementary nature of a pathway-based approach for genome-wide analysis of TGCT.

Hidden Y Chromosome Mosaicism in 48 Egyptian Patients with Turner’s Syndrome

Background. The presence of Y chromosome material in Turner's syndrome (TS) patients is a risk factor for the development of gonadoblastoma. Although conventional cytogenetic analysis is the definitive diagnosis of TS, low level Y chromosome mosaicism may be missed. Molecular analysis has demonstrated a higher proportion of mosaicism, but there is controversy regarding the prevalence of Y chromosome-derived material in those patients. Aim and Methods. This study was conducted to investigate the prevalence of hidden Y chromosome mosaicism in 48 TS Egyptian patients using polymerase chain reaction (PCR) for molecular DNA analysis of SRY gene and compare our results with those in the literature. Results. None of TS patients had a cytogenetically obvious Y chromosome; Y chromosome material was detected only at molecular analysis. SRY gene was found in 9 TS patients (18.75%) with the classical 45,X karyotype, whereas all other patients were SRY negative. Conclusion. Cytogenetically undetected Y chromosome mosaicism is common in TS patients; these data reinforce the need for adequate diagnosis of Y chromosome material in those patients. Molecular screening for Y chromosome-derived DNA should be routinely carried out in all TS patients.

A SRY-HMG box frame shift mutation inherited from a mosaic father with a mild form of testicular dysgenesis syndrome in Turner syndrome patient

BackgroundSex determining factor (SRY) located on the short arm of the Y chromosome, plays an important role in initiating male sex determination, resulting in development of testicular tissue. Presence of the SRY gene in females results in XY sex reversal and increased risk of gonadal germ cell tumours if the karyotype also includes the so-called GonadoBlastoma on the Y chromosome (GBY) region. The majority of mutations within the SRY gene are de novo affecting only a single individual in the family. The mutations within the high-mobility group (HMG) region have the potential to affect its DNA binding activity.Case PresentationWe performed G- and R-banding cytogenetic analysis of the patient and her family members including her father. We also performed molecular genetic analysis of SRY gene. Cytogenetic analysis in the patient (Turner Syndrome) revealed the mosaic karyotype as 45, X/46, XY (79%/21% respectively) while her father (milder features with testicular dysgenesis syndrome) has a normal male karyotype (46, XY). Using molecular approach, we screened the patient and her father for mutations in the SRY gene. Both patient and her father showed the same deletion of cytosine within HMG box resulting in frame shift mutation (L94fsX180), the father in a mosaic pattern. Histological examination of the gonads from the patient revealed the presence of gonadoblastoma formation, while the father presented with oligoasthenozoospermia and a testicular seminoma. The frameshift mutation at this codon is novel, and may result in a mutated SRY protein.ConclusionOur results suggest that lack of a second sex chromosome in majority cells of the patient may have triggered the short stature and primary infertility, and the mutated SRY protein may be associated with the development of gonadoblastoma. It is of importance to note that mosaic patients without a SRY mutation also have a risk for malignant germ cell tumors.

Y-chromosome markers in Turner syndrome: Screening of 130 patients

The presence of Y-chromosome material in patients with Turner syndrome (TS) is a risk factor for the development of gonadoblastoma. Cytogenetic analysis detects Y-chromosome mosaicism in about 5% of Turner patients. However, if Y-chromosome sequences are present in only a few cells, they may be missed by routine analysis. The use of molecular techniques to detect the presence of Y-chromosome fragments in such patients is becoming increasingly important. The objective of our study was to analyze cryptic Y-chromosome derivatives in Hungarian TS patient population by real-time PCR (RT-PCR). Cytogenetic and RT-PCR methods were used to examine peripheral blood DNA of 130 Hungarian patients with TS for the presence of Y-chromosome. With RT-PCR, 4 regions throughout the Y-chromosome were analyzed. Initial cytogenetic karyotyping assessing 10-50 metaphases revealed 3 patients with Y-chromosome positivity. RT-PCR revealed further 6 patients with Y-chromosome, who were initially considered as Y-negatives by standard kayotyping. The consecutive cytogenetic analysis of a large number (about 100) of metaphases (in 5 patients) and/or FISH (in 6 patients) however, also confirmed the presence of the Y-chromosome in these patients. Prophylactic gonadectomy was carried out in all 9 patients and 1 of them was diagnosed as having bilateral gonadoblastoma without clinical symptoms. We recommend a routine molecular screening for hidden Y-chromosome sequences in Turner patients, who are negative for Y-chromosome by conventional cytogenetic analysis, in order to calculate the future risk of developing gonadoblastoma.

Startling mosaicism of the Y-chromosome and tandem duplication of the SRY and DAZ genes in patients with Turner Syndrome.

Presence of the human Y-chromosome in females with Turner Syndrome (TS) enhances the risk of development of gonadoblastoma besides causing several other phenotypic abnormalities. In the present study, we have analyzed the Y chromosome in 15 clinically diagnosed Turner Syndrome (TS) patients and detected high level of mosaicisms ranging from 45,XO:46,XY = 100:0% in 4; 45,XO:46,XY:46XX = 4:94:2 in 8; and 45,XO:46,XY:46XX = 50:30:20 cells in 3 TS patients, unlike previous reports showing 5–8% cells with Y- material. Also, no ring, marker or di-centric Y was observed in any of the cases. Of the two TS patients having intact Y chromosome in >85% cells, one was exceptionally tall. Both the patients were positive for SRY, DAZ, CDY1, DBY, UTY and AZFa, b and c specific STSs. Real Time PCR and FISH demonstrated tandem duplication/multiplication of the SRY and DAZ genes. At sequence level, the SRY was normal in 8 TS patients while the remaining 7 showed either absence of this gene or known and novel mutations within and outside of the HMG box. SNV/SFV analysis showed normal four copies of the DAZ genes in these 8 patients. All the TS patients showed aplastic uterus with no ovaries and no symptom of gonadoblastoma. Present study demonstrates new types of polymorphisms indicating that no two TS patients have identical genotype-phenotype. Thus, a comprehensive analysis of more number of samples is warranted to uncover consensus on the loci affected, to be able to use them as potential diagnostic markers.

O hormônio de crescimento na síndrome de Turner: dados e reflexões

Short stature is the major characteristic of Turner syndrome. The statural appeal is premature and become evident in the puberty. Haploinsufficiency of SHOX gene has been related as main factor on final height of these patients. Despite the majority of the patients are not growth hormone deficient, the GHr therapy improves the final height. Recently, a great number of publications have described the association between GH and cancer. The cancer risk, in these patients, is mainly associated with the presence of Y chromosome sequences that can lead to the gonadoblastoma development. In conclusion, the GHr therapy in ST patients deserves caution. The investigation of Y chromosome sequences should be performed as well as the prophylactic gonadectomy in the positive cases conferring confidence to the treatment.

The Y-encoded TSPY protein: a significant marker potentially plays a role in the pathogenesis of testicular germ cell tumors

The testis-specific protein Y-encoded (TSPY) gene is the putative gene for the gonadoblastoma locus on the Y chromosome (GBY) that predisposes dysgenetic gonads of intersex patients to gonadoblastoma development. TSPY is expressed at high levels in gonadoblastoma tissues, supporting its possible oncogenic function in this type of germ cell tumors. To explore the possibility that this Y chromosome gene is also involved in pathogenesis of the more common testicular germ cell tumors (TGCTs), we have conducted various expression studies using immunohistochemistry, Western blotting, and reverse transcription-polymerase chain reaction analysis on 171 cases of TGCTs and selected normal testis controls. Our results demonstrated that TSPY protein is abundantly expressed in the precursor, carcinoma in situ or intratubular germ cell neoplasia unclassified, and seminoma, but only minimally or not expressed in various types of nonseminomas. TSPY coexpresses with established germ cell tumor markers (such as placental-like alkaline phosphatase, c-KIT, OCT4) and proliferative markers (such as Ki-67 and cyclin B1) in the same tumor cells at both RNA and protein levels. Ectopic TSPY expression in cultured cells up-regulates progrowth genes, including those at chromosome 12p13, frequently gained/amplified in TGCTs. Our results suggest that TSPY, in combination with other markers, could be an important marker for diagnosis and subclassification of TGCTs and support its role in the pathogenesis of both gonadoblastoma and TGCTs.

Testis-specific protein Y-encoded gene is expressed in early and late stages of gonadoblastoma and testicular carcinoma in situ

The testis-specific protein Y-encoded gene (TSPY) is a tandem repeat gene located at the critical region for the gonadoblastoma locus on Y chromosome that predisposes the dysgenetic gonads of intersex individuals to oncogenesis. The expression and molecular properties of TSPY suggest that it is the putative gene for the gonadoblastoma locus on Y chromosome. In this study, we examined the expression of TSPY and other germ cell tumor markers in 4 cases of gonadoblastoma using immunostaining techniques. Our results showed that TSPY expression was closely associated with initiation and various stages of gonadoblastoma development. TSPY protein localized with established germ cell tumor markers, such as the placental alkaline phosphatase, c-KIT, and OCT3/4, in the same tumor cells of both gonadoblastoma and adjacent carcinoma in situ, the precursor for germ cell tumors. These findings support the candidacy of TSPY as the gene for the gonadoblastoma locus on Y chromosome and suggest that TSPY could be a significant marker for these types of germ cell tumors.

Prophylactic bilateral salpingo-oopherectomy in a 17-year-old with Frasier syndrome reveals gonadoblastoma and seminoma: a case report

Mutations in the Wilms' tumor gene are present in children with Frasier syndrome, Denys-Drash syndrome, WAGR syndrome, and some cases of Wilms' tumor. The Wilms' tumor gene product, WT1, is necessary for normal urogenital development. Frasier syndrome is an association between focal segmental glomerulosclerosis, beginning in the second and third decade, male to female sex reversal, and dysgenetic gonads. We report a case of Frasier syndrome in a 17-year-old adolescent girl with renal failure, kidney transplant, and dysgenetic gonads, with development of gonadoblastoma and dysgerminoma (seminoma). The diagnosis of Frasier syndrome was based on nephrotic syndrome with diffuse mesangial sclerosis leading to chronic renal failure, dysgenetic gonads, 46 XY karyotype in a phenotypic female, and a mutation in the Wilms' tumor gene. Prophylactic laparoscopic bilateral salpingo-oopherectomy revealed gonadoblastoma and seminoma in opposite atrophic ovaries as well as a hypoplastic uterus. Early prophylactic resection of dysgenetic gonads is indicated in children with Frasier syndrome to prevent the development of germ cell malignancy.

Frasier syndrome in a pre-menarchal girl: laparoscopic resection of gonadoblastoma

Frasier syndrome (FS) is characterized by male pseudohermaphroditism, slowly progressing nephropathy, and frequent development of gonadoblastoma. These patients are, however, often diagnosed when evaluated for primary amenorrhea. We report the case of FS in a pre-menarchal girl at the age of 6 years. Ultrasound examinations were performed and were inconclusive as to the presence or size of the gonads. Diagnostic laparoscopy was performed and the presence of bilateral streak gonads was documented and a bilateral salpingo-oophorectomy was performed. The postoperative course was uneventful. Histological examination of the streak gonads confirmed the presence of gonadoblastoma. To our knowledge, this is the first case in the literature of a pre-menarchal patient diagnosed with FS and a laparoscopic bilateral gonadoblastoma resection. Laparoscopic aspects regarding safe streak gonad removal in the pediatric population have been elaborated.

Germ Cell Tumors in the Intersex Gonad: Old Paths, New Directions, Moving Frontiers

The risk for the development of germ cell tumors is an important factor to deal with in the management of patients with disorders of sex development (DSD). However, this risk is often hard to predict. Recently, major progress has been made in identifying gene-products related to germ cell tumor development (testis-specific protein-Y encoded and octamer binding transcription factor 3/4) and in recognizing early changes of germ cells (maturation delay, preneoplastic lesions, and in situ neoplasia). The newly recognized "undifferentiated gonadal tissue" has been identified as a gonadal differentiation pattern bearing a high risk for the development of gonadoblastoma. It is expected that the combination of these findings will allow for estimation of the risk for tumor development in the individual patient (high risk/intermediate risk/low risk). This article reviews the recent literature regarding the prevalence of germ cell tumors in patients with DSD. Some major limitations regarding this topic, including a confusing terminology referring to the different forms of intersex disorders and unclear criteria for the diagnosis of malignant germ cells at an early age (maturation delay vs. early steps in malignant transformation) are discussed. Thereafter, an overview of the recent advances that have been made in our knowledge of germ cell tumor development and the correct diagnosis of early neoplastic lesions in this patient population is provided. A new classification system for patients with DSD is proposed as a tool to refine our insight in the prevalence of germ cell tumors in specific diagnostic groups.

CK2-dependent C-terminal phosphorylation at T 300 directs the nuclear transport of TSPY protein

TSPY (testis-specific protein, Y-encoded) is a member of the greater SET/NAP family of molecules with various functions, e.g., in chromatin remodeling, regulation of gene expression, and has been implicated to play a role in the malignant development of gonadoblastoma, testicular and prostate cancer. Here we demonstrate that the C-terminus has a functional role for the nucleo-cytoplasmatic shuttling of the TSPY protein. Using various combinations of in vitro mutagenesis and enhanced green fluorescent protein reporter gene-expression experiments we were able to show that while the deletion of C-terminus leads to a decreased stability and enhanced degradation of the protein, the selective mutation of a C-terminal CK2 phosphorylation site (T 300) prevents the TSPY protein from entering the nucleus. We conclude that phosphorylation of the (T 300) residue is a necessary and functional prerequisite for TSPY’s transport into the nucleus reminding of comparable data from a related Drosophila molecule, NAP1.