Medline ® Abstract for Reference 66
of 'Lynch syndrome (hereditary nonpolyposis colorectal cancer): Clinical manifestations and diagnosis'
Human MLH1 deficiency predisposes to hematological malignancy and neurofibromatosis type 1.
Ricciardone MD, Ozçelik T, Cevher B, OzdağH, Tuncer M, Gürgey A, Uzunalimoğlu O, Cetinkaya H, Tanyeli A, Erken E, Oztürk M
Cancer Res. 1999;59(2):290.
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.
Department of Molecular Biology and Genetics, Faculty of Science, Bilkent University, Ankara, Turkey.