Expression of a candidate gene for the gonadoblastoma locus in gonadoblastoma and testicular seminoma

Lau, Yun‐Fai Chris; Chou, Pauline M.; Iezzoni, Julia C.; Alonzo, Judy; Kömüves, L.G.

doi:10.1159/000056838

Cited by 105 publications

(77 citation statements)

References 26 publications

(35 reference statements)

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“…Most of the hitherto known CT antigens have been mapped to the X chromosome with the exception of a few CT antigens that have been mapped to autosome (Scanlan et al, 2002;Lee et al, 2003;Loriot et al, 2003). Testis-specific protein Y-encoded gene was located on human proximal Yp, within the GBY (gonadoblastoma locus on the Y chromosome) critical region (Lau et al, 2000). Since HCC is three to four times more often in men than women (Kew, 2002;El-Serag, 2004), the relatively high frequency of TSPY in HCC patients might be of significance in aetiology and therapeutics.…”

Section: Discussionmentioning

confidence: 99%

TSPY is a cancer testis antigen expressed in human hepatocellular carcinoma

Qiao

et al. 2005

Br J Cancer

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In search for genes associated with hepatocellular carcinoma (HCC) by cDNA microarray, we found that the transcription of TSPY, 'testis-specific protein Y-encoded', was upregulated in HCC. Investigation of a broad spectrum of normal and malignant tissues by RT -PCR revealed the TSPY transcript selectively expressed in normal testis, different histological types of human neoplastic tissues, and tumour cell lines. The expression of TSPY in cancer cells was further confirmed by in situ hybridisation. Indirect immunofluorescence microscopy analysis showed that TSPY was localised mainly in the cytoplasm of transiently transfected cells. Testis-specific protein Y-encoded was detected in 50% (16 of 32) of well-and moderately differentiated HCC patients, in 16% (four of 25) of poorly differentiated HCC patients, and in 5% (one of 19) of renal cell cancer patients. A serological survey revealed that 6.6% (seven of 106) HCC patients had anti-TSPY antibody response, demonstrating the immunogenicity of TSPY in humans. In conclusion, these data suggest that TSPY is a novel cancer/testis (CT) antigen and may be a potential candidate in vaccine strategy for immunotherapy in HCC patients.

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Section: Discussionmentioning

confidence: 99%

TSPY is a cancer testis antigen expressed in human hepatocellular carcinoma

Qiao

et al. 2005

Br J Cancer

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“…20 The encoded protein is found to be highly expressed in CIS and GB. 21 In this study, we report a unique case of GB in a phenotypical adult woman of 26 years of age. In the DNA extracted from peripheral blood cells of this patient, a novel mutation was identified in the N-terminal NLS of SRY, resulting in reduced nuclear import, leading to gonadal dysgenesis.…”

Section: Introductionmentioning

confidence: 90%

A novel SRY missense mutation affecting nuclear import in a 46,XY female patient with bilateral gonadoblastoma

et al. 2009

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Patients with disorders of sex development (DSD), especially those with gonadal dysgenesis and hypovirilization, are at risk of developing the so-called type II germ cell tumors (GCTs). Both carcinoma in situ and gonadoblastoma (GB) can be the precursor lesion, resulting in a seminomatous or nonseminomatous invasive cancer. SRY mutations residing in the HMG domain are found in 10 -15% of 46,XY gonadal dysgenesis cases. This domain contains two nuclear localization signals (NLSs). In this study, we report a unique case of a phenotypical normal woman, diagnosed as a patient with 46,XY gonadal dysgenesis, with an NLS missense mutation, on the basis of the histological diagnosis of a unilateral GB. The normal role of SRY in gonadal development is the upregulation of SOX9 expression. The premalignant lesion of the initially removed gonad was positive for OCT3/4, TSPY and stem cell factor in germ cells, and for FOXL2 in the stromal component (ie, granulosa cells), but not for SOX9. On the basis of these findings, prophylactical gonadectomy of the other gonad was performed, also showing a GB lesion positive for both FOXL2 (ovary) and SOX9 (testis). The identified W70L mutation in the SRY gene resulted in a 50% reduction in the nuclear accumulation of the mutant protein compared with wild type. This likely explains the diminished SOX9 expression, and therefore the lack of proper Sertoli cell differentiation during development. This case shows the value of the proper diagnosis of human GCTs in identification of patients with DSD, which allows subsequent early diagnosis and prevention of the development of an invasive cancer, likely to be treated by chemotherapy at young age.

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“…In the fetal gonad TSPY protein is expressed at a constant level (Honecker et al, 2004). However TSPY protein becomes more abundant compared to both normal embryonic and adult testis, in CIS, GB and sporadically in seminoma (Lau et al, 2000). TSPY is homologous to SET/NAP proteins, which play a role in nucleosome assembly and chromatin remodelling (Wagner et al, 2006).…”

Section: Oct3/4 Biology and Diagnostic Markermentioning

confidence: 99%