Gonadoblastomas in 45,X/46,XY Mosaicism:<i>Analysis of Y Chromosome Distribution by Fluorescence In Situ Hybridization</i>

Iezzoni, Julia C.; Kap-Herr, C. Von; Golden, Wendy L.; Gaffey, M. J.

doi:10.1093/ajcp/108.2.197

Cited by 30 publications

(19 citation statements)

References 12 publications

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“…A higher proportion of XY cells were observed within the tumors compared with the dysgenetic gonads ( Table 2). Our data obtained by FISH analysis demonstrated that the sex chromosomes of mosaic patients do not distribute homogenously in dysgenetic gonads as was previously described 3 and confirms the original findings reported by Iezzoni et al 34 where the proportion of the XY cell line was higher in the tumor than in the stromal cells. These authors proposed that the presence of Y-chromosome material participates in the pathogenesis of the tumor.…”

Section: Discussionsupporting

confidence: 92%

Distribution of Y-chromosome-bearing cells in gonadoblastoma and dysgenetic testis in 45,X/46,XY infants

et al. 2005

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Gonadoblastoma is an unusual mixed germ cell-sex cord-stromal tumor that has the potential for malignant transformation and 30% of all patients with gonadoblastoma develop germ cell tumors mainly dysgerminoma/ seminoma. An additional 10% gives rise to other malignant germ cell neoplasms. This tumor affects a subset of patients with intersex disorders. The age at diagnosis is variable ranging from birth to the fourth decade, but around 94% of cases are diagnosed during the first three decades of life and there are few cases with gonadoblastoma diagnosed in infants. In this paper, we present the histological and molecular findings of four patients with gonadal dysgenesis who developed gonadoblastoma in the first 2 years of life and one case with bilateral dysgerminoma diagnosed at 15 years of age. The sex chromosomes of mosaic patients do not distribute homogenously in dysgenetic gonads; however, statistical analysis of FISH results revealed significant differences between the XY cell line in the gonadoblastoma compared with the dysgenetic testis. Our cases demonstrate that tumors could be present at a very early age, so the prophylactic removal of the gonads is advised.

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Section: Discussionsupporting

confidence: 92%

Distribution of Y-chromosome-bearing cells in gonadoblastoma and dysgenetic testis in 45,X/46,XY infants

et al. 2005

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“…One of our patient with bilateral gonadoblastoma had no mosaicism for Y-chromosome in one of the gonads, while it has been suggested that the gonadal karyotype, rather than that of lymphocytes or skin, determines the risk of malignancy [Scully, 1970;Verp and Simpson, 1987]. In patients with 45,X/46,XY mosaicism Iezzoni et al [1997] found a higher proportion of nuclei with a Y-chromosome signal in the gonadoblastoma tumor cells than in the surrounding nontumor stromal cells.…”

Section: Discussionmentioning

confidence: 48%

Gonadoblastoma in Turner syndrome and Y‐chromosome‐derived material

Mazzanti

Cicognani

Baldazzi

et al. 2005

American J of Med Genetics Pt A

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The identification of Y-chromosome material is important in females with Ullrich-Turner syndrome (UTS) due to the risk of developing gonadoblastoma or other gonadal tumors. There is controversy regarding the frequency of the Y-chromosome-derived material and the occurrence of gonadoblastoma in these patients. The aim of our study was to evaluate a large number of patients with UTS, followed before and during the pubertal age for the prevalence of Y-chromosome derived material, the occurrence of gonadoblastoma, and the incidence of possible neoplastic degeneration. An unselected series of 171 patients with UTS (1-34 years old), diagnosed cytogenetically, was studied for Y-chromosome markers (SRY and Y-centromeric DYZ3 repeats). The follow-up was of 2-22 years; 101 of these patients were followed during pubertal age. Y-chromosome material was found in 14 patients (8%): 12 of these were gonadectomized (2.8-25.9 years). A gonadoblastoma was detected in four patients under 16 years of age: in two, Y-material was detected only at molecular analysis (at conventional cytogenetic analysis, one was included in the 45,X group and one in the X + mar group) and one had also an immature teratoma and an endodermal sinus carcinoma. The prevalence of gonadoblastoma in our series of gonadectomized UTS patients with Y-positive material was of 33.3% (4/12). Our data suggest that the age of appearance and the possibility of malignant degeneration of gonadoblastoma can occur early in life. These patients, in particular those with 45,X or a marker chromosome may benefit from molecular screening to detect the presence of Y-chromosome material; PCR is a rapid and inexpensive technique. At the moment, laparoscopy and preventive gonadectomy performed as soon as possible remain the procedures of choice for patients with UTS, when Y-chromosome has been identified, as we are still unable to predict a future malignant evolution of gonadoblastoma.

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“…These tumors are infrequent and are not found in normal males or females. However, in 46,XY testicular feminization patients, or in 47,XXY or 46,XX males (all of whom have a testis devoid of germ cells), gonadoblastomas develop in greater than 30 % of the phenotypic females who carry some Y-chromosome materials in their genome (Verp and Simpson, 1987;Sultana et al, 1995;Iezzoni et al, 1997). According to these observations, Page (1987) postulated the existence of a GBY locus on the Y chromosome that predisposes the dysgenic gonads of XY sexreversed females to develop gonadoblastomas.…”

Section: Discussionmentioning

confidence: 99%

SRY protein is expressed in ovotestis and streak gonads from human sex-reversal

Salas-Cortes

Jaubert

Nihoul‐Feketé

et al. 2000

Cytogenet Genome Res

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In mammals, a master gene located on the Y chromosome, the testis-determining gene SRY, controls sex determination. SRY protein is expressed in the genital ridge before testis determination, and in the testis it is expressed in Sertoli and germ cells. Completely sex-reversed patients are classified as either 46,XX males or 46,XY females. SRY mutations have been described in only 15% of patients with 46,XY complete or partial gonadal dysgenesis. However, although incomplete or partial sex-reversal affects 46,XX true hermaphrodites, 46,XY gonadal dysgenesis, and 46,XX/46,XY mosaicism, only 15% of the 46,XX true hermaphrodites analyzed have the SRY gene. Here, we demonstrate that the SRY protein is expressed in the tubules of streak gonads and rete testis, indicating that the SRY protein is normally expressed early during testis determination. Based on these results, we propose that some factors downstream from SRY may be mutated in these 46,XY sex-reversal patients. We have also analyzed SRY protein expression in the ovotestis from 46,XX true hermaphrodites and 46,XX/46,XY mosaicism, demonstrating SRY protein expression in both testicular and ovarian portions in these patients. This suggests that the SRY protein does not inhibit ovary development. These results confirm that other factors are needed for complete testis development, in particular, those downstream of the SRY protein.

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Gonadoblastomas in 45,X/46,XY Mosaicism:Analysis of Y Chromosome Distribution by Fluorescence In Situ Hybridization

Cited by 30 publications

References 12 publications

Distribution of Y-chromosome-bearing cells in gonadoblastoma and dysgenetic testis in 45,X/46,XY infants

Distribution of Y-chromosome-bearing cells in gonadoblastoma and dysgenetic testis in 45,X/46,XY infants

Gonadoblastoma in Turner syndrome and Y‐chromosome‐derived material

SRY protein is expressed in ovotestis and streak gonads from human sex-reversal

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