Identification of a rare MET variant in three siblings with extramammary Paget disease.
Yuki KobyashiYoshio NakamuraUmi TaharaKohei NakamuraKuniaki NakanishiAkihiro MiyagawaHiroto HorikawaKenta KobayashiTakeru FunakoshiKokichi SuganoMineko UshiamaTeruhiko YoshidaToyoko InazumiPublished in: Clinical and experimental dermatology (2024)
Extramammary Paget disease (EMPD) is an intraepithelial adenocarcinoma that primarily affects the genital and axillary areas in older individuals. A limited number of paired patients with familial EMPD (i.e. parent-offspring, siblings) have been reported but the genetics have not yet been adequately studied. We report, to the best of our knowledge, the first familial cases of patients with EMPD involving three affected siblings. The tumour-only multigene panel testing using surgical specimens revealed a heterozygous c.2997A>C (p.Glu999Asp) nonsynonymous variant in the proto-oncogene MET (NM_000245.4) in the three affected siblings. The germline multigene panel testing using peripheral blood lymphocytes revealed the same missense MET variant in all five family members who were tested, including two asymptomatic offspring (51 and 37 years of age). The MET variant we identified could be involved in EMPD carcinogenesis. Further genomic analyses of patients with familial EMPD are warranted to validate the pathogenic relevance of MET variants in EMPD development.
Keyphrases
- intellectual disability
- tyrosine kinase
- peripheral blood
- early onset
- high fat diet
- copy number
- autism spectrum disorder
- squamous cell carcinoma
- high grade
- physical activity
- photodynamic therapy
- radiation therapy
- type diabetes
- neoadjuvant chemotherapy
- skeletal muscle
- metabolic syndrome
- sentinel lymph node
- bioinformatics analysis
- community dwelling
- genome wide