Human MLH1 deficiency predisposes to hematological malignancy and neurofibromatosis type 1

Ricciardone M., Ozcelik T., Cevher B., Ozdag H., Tuncer M., Gurgey A., ...More

CANCER RESEARCH, vol.59, no.2, pp.290-293, 1999 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 59 Issue: 2
  • Publication Date: 1999
  • Title of Journal : CANCER RESEARCH
  • Page Numbers: pp.290-293


Heterozygous germ-line mutations in the DNA mismatch repair genes lead to hereditary nonpolyposis colorectal cancer, The disease susceptibility of individuals who constitutionally lack both wild-type alleles is unknown. We have identified three offspring in a hereditary nonpolyposis colorectal cancer family who developed hematological malignancy at a very early age, and at least two of them displayed signs of neurofibromatosis type 1(NF1), DNA sequence analysis and allele-specific amplification in two siblings revealed a homozygous MLH1 mutation (C676T-->Arg226Stop). Thus, a homozygous germ-line MLH1 mutation and consequent mismatch repair deficiency results in a mutator phenotype characterized by leukemia and/or lymphoma associated with neurofibromatosis type 1.