Combined germline pathogenic variants in FLCN and TP53 are associated with early onset renal cell carcinoma and brain tumors

Abstract

Background We present a family consisting of a father and his two children with an exceptional phenotype of childhood renal cell carcinoma and brain tumors. Extensive genetic testing revealed two inherited tumor predisposition syndromes in all three family members: Birt‐Hogg‐Dubé syndrome and Li‐Fraumeni syndrome. The corresponding genes ( FLCN and TP53 ) are both located on the short arm of chromosome 17. Methods We describe the phenotype and performed single nucleotide polymorphism (SNP)‐based loss of heterozygosity (LOH) analysis of the tumors. Results All examined tumors showed somatic loss of the wild‐type alleles of both FLCN and TP53 . Conclusions We hypothesize that a synergistic effect of both mutations caused the unusual phenotype of childhood renal cell carcinoma in this family. This family emphasizes the importance of further genetic testing if a tumor develops at an unexpected young age in an inherited cancer predisposition syndrome.

Hereditary cancer syndromes with increased risk of renal cancer

“…Расширение возможностей генетического тестирования и повсеместное применение ВПС приводят иногда к выявлению нетипичных семей с НОС, в которых манифестация заболевания обусловлена мутациями 2 и более патогенных вариантов в генах-кандидатах различных онкосиндромов. Так, описана семья с мутациями в генах FLCN и ТР53, в которой у носителей мутаций в 2 генах с детского возраста диагностировали РП и опухоли головного мозга [56]…”