Identification of a rare MET variant in a familial case of extramammary Paget's disease.
Yuki KobyashiYoshio NakamuraUmi TaharaKohei NakamuraKuniaki NakanishiAkihiro MiyagawaHiroto HorikawaKenta KobayashiTakeru FunakoshiKokichi SuganoMineko UshiamaTeruhiko YoshidaToyoko InazumiPublished in: Clinical and experimental dermatology (2024)
Extramammary Paget's disease (EMPD) is an intraepithelial adenocarcinoma that primarily affects the genital and axillary areas in elderly individuals. A limited number of paired familial EMPD cases (i.e., parent-offspring, siblings) have been reported, whereas the genetics of these cases have not yet been adequately studied. We report the first familial case of EMPD involving three affected siblings. The tumour-only multi-gene 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 multi-gene panel testing using peripheral blood lymphocytes revealed the same missense MET variant in all five family members, including the two asymptomatic offspring (51 and 37 years of age). The MET variant we identified could be involved in EMPD carcinogenesis. Further genomic analyses of familial cases of EMPD are warranted to validate the pathogenic relevance of MET variants in EMPD development.
Keyphrases
- early onset
- tyrosine kinase
- peripheral blood
- copy number
- intellectual disability
- high fat diet
- genome wide
- lymph node
- single cell
- gene expression
- high grade
- autism spectrum disorder
- photodynamic therapy
- dna repair
- adipose tissue
- neoadjuvant chemotherapy
- skeletal muscle
- metabolic syndrome
- ultrasound guided
- insulin resistance
- early stage
- genome wide identification
- fine needle aspiration
- solid state