ArticleThe Journal of clinical endocrinology and metabolism2013
Cyclic AMP and c-KIT signaling in familial testicular germ cell tumor predisposition.
Article in The Journal of clinical endocrinology and metabolism, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00034424 (Multidisciplinary Etiologic Study of Familial Testicular Cancer), which is not on this map. Cited by 12 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Multidisciplinary Etiologic Study of Familial Testicular Cancer
Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.
- Association between KITLG Gene Polymorphisms and Testicular Germ Cell Tumors: A Systematic Review and Meta-analysis.Current medical science · 2019Pooled it
- Family-Based Study RevealsInternational journal of molecular sciences · 2026Article
- PDE11A Is a Phenotype Modulator of Primary Bilateral Macronodular Adrenal Hyperplasia: Results of a 334-Patient Series.The Journal of clinical endocrinology and metabolism · 2025Article
- Once upon a Testis: The Tale of Cyclic Nucleotide Phosphodiesterase in Testicular Cancers.International journal of molecular sciences · 2023Review
- The cAMP-signaling cancers: Clinically-divergent disorders with a common central pathway.Frontiers in endocrinology · 2022Review
- Phosphodiesterase 2A and 3B variants are associated with primary aldosteronism.Endocrine-related cancer · 2021Article
- c-KIT oncogene expression in PRKAR1A-mutant adrenal cortex.Endocrine-related cancer · 2020Article
- Genetic changes associated with testicular cancer susceptibility.Seminars in oncology · 2016Review
- Male Reproductive Disorders and Fertility Trends: Influences of Environment and Genetic Susceptibility.Physiological reviews · 2016Review
- Rare inactivating PDE11A variants associated with testicular germ cell tumors.Endocrine-related cancer · 2015Article
- Nontesticular cancers in relatives of testicular germ cell tumor (TGCT) patients from multiple-case TGCT families.Cancer medicine · 2015Article
- Genome wide DNA methylation profiles provide clues to the origin and pathogenesis of germ cell tumors.PloS one · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundFamilial testicular germ cell tumors (FTGCTs) are hypothesized to result from the combined interaction of multiple low-penetrance genes. We reported inactivating germline mutations of the cAMP-binding phosphodiesterase 11A (PDE11A) as modifiers of FTGCT risk. Recent genome-wide association studies have identified single-nucleotide polymorphisms in the KITLG gene, the ligand for the cKIT tyrosine kinase receptor, as strong modifiers of susceptibility to both familial and sporadic testicular germ cell tumors.
designWe studied 94 patients with FTGCTs and 50 at-risk male relatives from 63 unrelated kindreds, in whom the PDE11A gene had been sequenced by investigating the association between KITLG genome-wide association study single-nucleotide polymorphisms rs3782179 and rs4474514 and FTGCT risk in these patients and in 692 controls. We also examined cAMP and c-KIT signaling in testicular tissues and cell lines and extended the studies to 2 sporadic cases, one with a PDE11A defect and one without, as a comparison.
resultsWe found a higher frequency of the KITLG risk alleles in FTGCT patients who also had a PDE11A sequence variant, compared with those with a wild-type PDE11A sequence. In NTERA-2 and Tcam-2 cells transfected with the mutated forms of PDE11A (R52T, F258Y, Y727C, R804H, V820M, R867G, and M878V), cAMP levels were significantly higher, and the relative phosphodiesterase activity was lower than in the wild-type cells. KITLG expression was consistently increased in the presence of PDE11A-inactivating defects, both at the RNA and protein levels, in familial testicular germ cell tumors. The 2 sporadic cases that were studied, one with a PDE11A defect and another without, agreed with the data in FTGTCT and in the cell lines.
conclusionsPatients with FTGCT and PDE11A defects also carry KITLG risk alleles more frequently. There may be an interaction between cAMP and c-KIT signaling in predisposition to testicular germ cell tumors.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.