| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
Submitted on January 26, 2006
Accepted on May 25, 2006
Molecular and Population Genetics Laboratory (L.G.C-C., N.A.A., P.J.P., A.M.J., E.B., N.W., I.P.M.T.) and Histopathology Unit and In Situ Hybridisation Service (R.H.), London Research Institute, Cancer Research UK, London, United Kingdom; Department of Pathology and Microbiology, Division of Histopathology, Bristol Royal Infirmary (M.P.), Bristol, United Kingdom; Department of Pathology, University College Hospital (A.F.), London, United Kingdom; Department of Pathology, Kings College Hospital (S.P.), London, United Kingdom; Department of Histopathology, Nottingham City Hospital (I.E.), Nottingham, United Kingdom; Department of Histopathology, Division of Investigative Science, Imperial College (M.A.E-B.), London, United Kingdom; Department of Pathology, St Bartholomew's Hospital (D.M.B.), London, United Kingdom
* To whom correspondence should be addressed. E-mail: luis.carvajal{at}cancer.org.uk.
Context: Leydig-cell tumors (LCTs) are the most common non-germ cell neoplasms of the testis. LCTs are often hormonally active and can result in precocious virilisation or in adult feminisation. We identified a LCT in an affected individual from a kindred with hereditary leiomyomatosis and renal cell cancer (HLRCC) and a germline fumarate hydratase (FH) mutation (N64T).
Objective: To investigate the role of FH mutations in predisposition to LCTs.
Design: We tested for pathogenic effects of the N64T mutation and screened a further 29 unselected LCTs for FH alterations. We also tested these LCTs for mutations in two genes, the LH/choriogonadotropin receptor (LHCGR) and the guanine nucleotide binding protein 
(GNAS) that had been implicated in LCT tumorigenesis.
Results: No mutations were found in GNAS and one tumor had a LHCGR somatic substitution. In addition to the HLRCC case with the N64T germline FH mutation, we identified one other LCT with a previously unreported FH mutation (M411I). Both LCTs from these patients showed loss of the wild-type FH allele. Immunohistochemical and in situ hybridization analyses demonstrated activation of the hypoxia/angiogenesis pathway not only in the tumors belonging to the FH mutation carriers, but also in several other mutation-negative LCTs.
Conclusions: Our study shows that some LCTs are caused by FH mutations and represents one of the first reports of germline mutations in any type of adult testicular tumor.
This article has been cited by other articles:
 |
|
 |
|
  J. A. Mayr, D. Meierhofer, F. Zimmermann, R. Feichtinger, C. Kogler, M. Ratschek, N. Schmeller, W. Sperl, and B. Kofler Loss of Complex I due to Mitochondrial DNA Mutations in Renal Oncocytoma Clin. Cancer Res., April 15, 2008; 14(8): 2270 - 2275. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
