Heterozygote FANCD2 mutations associated with childhood T Cell ALL and testicular seminoma

Fam Cancer. 2012 Dec;11(4):661-5. doi: 10.1007/s10689-012-9553-3.

Abstract

Fanconi anaemia (FA) is an inherited disease with congenital and developmental abnormalities characterised by cellular cross linker hypersensitivity. FA is caused by mutations in any of so far 15 identified FANC genes, which encode proteins that interact in a common DNA damage response (DDR) pathway. Individuals with FA have a high risk of developing acute myeloid leukaemia (AML) and squamous cell carcinoma. An increased cancer risk has been firmly established for carriers of mutations in FANCD1/BRCA2, FANCJ/BRIP1, FANCN/PALB2, RAD51C/FANCO and link the FA pathway to inherited breast and ovarian cancer. We describe a pedigree with FANCD2 mutations c.458T > C (p.Leu153Ser) and c.2715 + 1G > A (p.Glu906LeufsX4) with mild phenotype FA in the index case, T cell ALL in the Leu153Ser heterozygous brother and testicular seminoma in the p.Glu906LeufsX4 heterozygous father. Both FANCD2 alleles were present in the T Cell ALL and the seminoma. This links specific FANCD2 mutations to T cell ALL and seminoma without evidence of allelic loss in the tumour tissue.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Child
  • Child, Preschool
  • Fanconi Anemia / genetics
  • Fanconi Anemia Complementation Group D2 Protein / genetics*
  • Fanconi Anemia Complementation Group D2 Protein / metabolism
  • Female
  • Heterozygote
  • Humans
  • Immunoenzyme Techniques
  • Male
  • Mutation / genetics*
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / metabolism
  • Prognosis
  • Seminoma / genetics*
  • Seminoma / metabolism
  • Testicular Neoplasms / genetics*
  • Testicular Neoplasms / metabolism

Substances

  • FANCD2 protein, human
  • Fanconi Anemia Complementation Group D2 Protein