ArticleNature genetics2009
Activating mutations in FGFR3 and HRAS reveal a shared genetic origin for congenital disorders and testicular tumors.
Article in Nature genetics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers.
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.
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Who cites it
95 citing papers in PubMed, 206 citations in OpenAlex.
- Spermatocytic Tumor Arising in a Cryptorchid Testis: A Case Report and Narrative Review.Journal of clinical medicine · 2026Review
- Stem cell competition.Current topics in developmental biology · 2026Review
- Article
- Development of a Clinically Applicable High-Resolution Assay for Sperm Mosaicism.The Journal of molecular diagnostics : JMD · 2025Article
- Spermatocytic tumor coexisting with a contralateral inguinoscrotal undifferentiated sarcoma: a case report.BMC urology · 2025Article
- Expert Consensus on the Diagnosis and Treatment of FGFR Gene-Altered Solid Tumors.Global medical genetics · 2024Review
- Paternal age, de novo mutations, and offspring health? New directions for an ageing problem.Human reproduction (Oxford, England) · 2024Review
- Mechanisms of Germline Stem Cell Competition across Species.Life (Basel, Switzerland) · 2024Review
- SMAD4 mutations causing Myhre syndrome are under positive selection in the male germline.American journal of human genetics · 2024Article
- [Sperm Mosaic Variants and Their Influence on the Offspring].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2024Review
- Exploring FGFR3 Mutations in the Male Germline: Implications for Clonal Germline Expansions and Paternal Age-Related Dysplasias.Genome biology and evolution · 2024Article
- Exploring the Micro-Mosaic Landscape ofGenes · 2024Article
- SPRY4-dependent ERK negative feedback demarcates functional adult stem cells in the male mouse germline†.Biology of reproduction · 2023Article
- The impact of paternal age on new mutations and disease in the next generation.Fertility and sterility · 2022Review
- Article
- FGFR3 is expressed by human primordial germ cells and is repressed after meiotic initiation to form primordial oocytes.Stem cell reports · 2022Article
- Discovery of an unusually high number of de novo mutations in sperm of older men using duplex sequencing.Genome research · 2022Article
- Review
- Signaling Pathway and Small-Molecule Drug Discovery of FGFR: A Comprehensive Review.Frontiers in chemistry · 2022Review
- Development and validation of an expanded targeted sequencing panel for non-invasive prenatal diagnosis of sporadic skeletal dysplasia.BMC medical genomics · 2021Article
35 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
Genes mutated in congenital malformation syndromes are frequently implicated in oncogenesis, but the causative germline and somatic mutations occur in separate cells at different times of an organism's life. Here we unify these processes to a single cellular event for mutations arising in male germ cells that show a paternal age effect. Screening of 30 spermatocytic seminomas for oncogenic mutations in 17 genes identified 2 mutations in FGFR3 (both 1948A>G, encoding K650E, which causes thanatophoric dysplasia in the germline) and 5 mutations in HRAS. Massively parallel sequencing of sperm DNA showed that levels of the FGFR3 mutation increase with paternal age and that the mutation spectrum at the Lys650 codon is similar to that observed in bladder cancer. Most spermatocytic seminomas show increased immunoreactivity for FGFR3 and/or HRAS. We propose that paternal age-effect mutations activate a common 'selfish' pathway supporting proliferation in the testis, leading to diverse phenotypes in the next generation including fetal lethality, congenital syndromes and cancer predisposition.
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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.