Skip to main content
PMC home page
American Journal of Human Genetics logoLink to American Journal of Human Genetics
. 1995 Dec;57(6):1400–1407.

Gonadoblastoma: molecular definition of the susceptibility region on the Y chromosome.

K Tsuchiya 1, R Reijo 1, D C Page 1, C M Disteche 1
PMCID: PMC1801429  PMID: 8533770

Abstract

Using sequence-tagged sites we have performed deletion mapping of the Y chromosome in sex-reversed female patients with a Y chromosome and gonadoblastoma. The GBY gene (gonadoblastoma locus on the Y chromosome) was sublocalized to a small region near the centromere of the Y chromosome. We estimate the size of the GBY critical region to be approximately 1-2 Mb. Our analysis also indicates that copies of two dispersed Y-linked gene families, TSPY (testis-specific protein, Y-encoded) and YRRM (Y-chromosome RNA recognition motif) are present in all patients and that copies of TSPY but not YRRM fall within the GBY critical region as formally defined by deletion mapping. Two tumor samples showed expression of both genes and in one patient this expression was limited to a unilateral gonadoblastoma but absent in the contralateral streak gonad. Although our results do not directly implicate TSPY or YRRM in the etiology of the tumor, they raise the issue of whether there is one GBY gene in the critical region or possibly multiple GBY loci dispersed on the Y chromosome.

Full text

PDF
1402

Images in this article

1403Figure 2
on p.1403
1404Figure 4
on p.1404
1405Figure 5
on p.1405

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adler D. A., Bressler S. L., Chapman V. M., Page D. C., Disteche C. M. Inactivation of the Zfx gene on the mouse X chromosome. Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):4592–4595. doi: 10.1073/pnas.88.11.4592. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Arnemann J., Epplen J. T., Cooke H. J., Sauermann U., Engel W., Schmidtke J. A human Y-chromosomal DNA sequence expressed in testicular tissue. Nucleic Acids Res. 1987 Nov 11;15(21):8713–8724. doi: 10.1093/nar/15.21.8713. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Arnemann J., Jakubiczka S., Thüring S., Schmidtke J. Cloning and sequence analysis of a human Y-chromosome-derived, testicular cDNA, TSPY. Genomics. 1991 Sep;11(1):108–114. doi: 10.1016/0888-7543(91)90107-p. [DOI] [PubMed] [Google Scholar]
  4. Cantrell M. A., Bicknell J. N., Pagon R. A., Page D. C., Walker D. C., Saal H. M., Zinn A. B., Disteche C. M. Molecular analysis of 46,XY females and regional assignment of a new Y-chromosome-specific probe. Hum Genet. 1989 Aug;83(1):88–92. doi: 10.1007/BF00274156. [DOI] [PubMed] [Google Scholar]
  5. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  6. Disteche C. M., Casanova M., Saal H., Friedman C., Sybert V., Graham J., Thuline H., Page D. C., Fellous M. Small deletions of the short arm of the Y chromosome in 46,XY females. Proc Natl Acad Sci U S A. 1986 Oct;83(20):7841–7844. doi: 10.1073/pnas.83.20.7841. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Disteche C. M., Saal H., Friedman C., Sybert V., Thuline H. Quantitative analysis of sex-chromosome mosaicism with X-Y DNA probes. Am J Hum Genet. 1986 May;38(5):751–758. [PMC free article] [PubMed] [Google Scholar]
  8. Foote S., Vollrath D., Hilton A., Page D. C. The human Y chromosome: overlapping DNA clones spanning the euchromatic region. Science. 1992 Oct 2;258(5079):60–66. doi: 10.1126/science.1359640. [DOI] [PubMed] [Google Scholar]
  9. Hawkins J. R., Taylor A., Goodfellow P. N., Migeon C. J., Smith K. D., Berkovitz G. D. Evidence for increased prevalence of SRY mutations in XY females with complete rather than partial gonadal dysgenesis. Am J Hum Genet. 1992 Nov;51(5):979–984. [PMC free article] [PubMed] [Google Scholar]
  10. Kawasaki E. S., Clark S. S., Coyne M. Y., Smith S. D., Champlin R., Witte O. N., McCormick F. P. Diagnosis of chronic myeloid and acute lymphocytic leukemias by detection of leukemia-specific mRNA sequences amplified in vitro. Proc Natl Acad Sci U S A. 1988 Aug;85(15):5698–5702. doi: 10.1073/pnas.85.15.5698. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Ma K., Inglis J. D., Sharkey A., Bickmore W. A., Hill R. E., Prosser E. J., Speed R. M., Thomson E. J., Jobling M., Taylor K. A Y chromosome gene family with RNA-binding protein homology: candidates for the azoospermia factor AZF controlling human spermatogenesis. Cell. 1993 Dec 31;75(7):1287–1295. doi: 10.1016/0092-8674(93)90616-x. [DOI] [PubMed] [Google Scholar]
  12. Magenis R. E., Casanova M., Fellous M., Olson S., Sheehy R. Further cytologic evidence for Xp-Yp translocation in XX males using in situ hybridization with Y-derived probe. Hum Genet. 1987 Mar;75(3):228–233. doi: 10.1007/BF00281064. [DOI] [PubMed] [Google Scholar]
  13. Magenis R. E., Tochen M. L., Holahan K. P., Carey T., Allen L., Brown M. G. Turner syndrome resulting from partial deletion of Y chromosome short arm: localization of male determinants. J Pediatr. 1984 Dec;105(6):916–919. doi: 10.1016/s0022-3476(84)80077-3. [DOI] [PubMed] [Google Scholar]
  14. Manz E., Schnieders F., Brechlin A. M., Schmidtke J. TSPY-related sequences represent a microheterogeneous gene family organized as constitutive elements in DYZ5 tandem repeat units on the human Y chromosome. Genomics. 1993 Sep;17(3):726–731. doi: 10.1006/geno.1993.1393. [DOI] [PubMed] [Google Scholar]
  15. Page D. C. Hypothesis: a Y-chromosomal gene causes gonadoblastoma in dysgenetic gonads. Development. 1987;101 (Suppl):151–155. doi: 10.1242/dev.101.Supplement.151. [DOI] [PubMed] [Google Scholar]
  16. Pearson W. R., Lipman D. J. Improved tools for biological sequence comparison. Proc Natl Acad Sci U S A. 1988 Apr;85(8):2444–2448. doi: 10.1073/pnas.85.8.2444. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Petrovic V., Nasioulas S., Chow C. W., Voullaire L., Schmidt M., Dahl H. Minute Y chromosome derived marker in a child with gonadoblastoma: cytogenetic and DNA studies. J Med Genet. 1992 Aug;29(8):542–546. doi: 10.1136/jmg.29.8.542. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Reijo R., Lee T. Y., Salo P., Alagappan R., Brown L. G., Rosenberg M., Rozen S., Jaffe T., Straus D., Hovatta O. Diverse spermatogenic defects in humans caused by Y chromosome deletions encompassing a novel RNA-binding protein gene. Nat Genet. 1995 Aug;10(4):383–393. doi: 10.1038/ng0895-383. [DOI] [PubMed] [Google Scholar]
  19. Scully R. E. Gonadoblastoma. A review of 74 cases. Cancer. 1970 Jun;25(6):1340–1356. doi: 10.1002/1097-0142(197006)25:6<1340::aid-cncr2820250612>3.0.co;2-n. [DOI] [PubMed] [Google Scholar]
  20. Tyler-Smith C., Oakey R. J., Larin Z., Fisher R. B., Crocker M., Affara N. A., Ferguson-Smith M. A., Muenke M., Zuffardi O., Jobling M. A. Localization of DNA sequences required for human centromere function through an analysis of rearranged Y chromosomes. Nat Genet. 1993 Dec;5(4):368–375. doi: 10.1038/ng1293-368. [DOI] [PubMed] [Google Scholar]
  21. Vergnaud G., Page D. C., Simmler M. C., Brown L., Rouyer F., Noel B., Botstein D., de la Chapelle A., Weissenbach J. A deletion map of the human Y chromosome based on DNA hybridization. Am J Hum Genet. 1986 Feb;38(2):109–124. [PMC free article] [PubMed] [Google Scholar]
  22. Verp M. S., Simpson J. L. Abnormal sexual differentiation and neoplasia. Cancer Genet Cytogenet. 1987 Apr;25(2):191–218. doi: 10.1016/0165-4608(87)90180-4. [DOI] [PubMed] [Google Scholar]
  23. Vollrath D., Foote S., Hilton A., Brown L. G., Beer-Romero P., Bogan J. S., Page D. C. The human Y chromosome: a 43-interval map based on naturally occurring deletions. Science. 1992 Oct 2;258(5079):52–59. doi: 10.1126/science.1439769. [DOI] [PubMed] [Google Scholar]
  24. Zhang J. S., Yang-Feng T. L., Muller U., Mohandas T. K., de Jong P. J., Lau Y. F. Molecular isolation and characterization of an expressed gene from the human Y chromosome. Hum Mol Genet. 1992 Dec;1(9):717–726. doi: 10.1093/hmg/1.9.717. [DOI] [PubMed] [Google Scholar]
  25. von Lindern M., van Baal S., Wiegant J., Raap A., Hagemeijer A., Grosveld G. Can, a putative oncogene associated with myeloid leukemogenesis, may be activated by fusion of its 3' half to different genes: characterization of the set gene. Mol Cell Biol. 1992 Aug;12(8):3346–3355. doi: 10.1128/mcb.12.8.3346. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from American Journal of Human Genetics are provided here courtesy of American Society of Human Genetics

RESOURCES