Germline mutations of the perforin gene are a frequent occurrence in childhood anaplastic large cell lymphoma

Cancer. 2007 Jun 15;109(12):2566-71. doi: 10.1002/cncr.22718.


Background: Monoallelic and biallelic mutations of the PRF1 gene have been reported in some cases of childhood lymphoma. Anaplastic large cell lymphoma (ALCL) accounts for 10% to 15% of all childhood lymphomas. To assess the possible role of PRF1 mutations in ALCL, the authors screened a series of patients collected by the Associazione Italiana di Ematologia Oncologia Pediatrica (AIEOP).

Methods: The authors investigated 44 patients with ALCL by direct sequence of the PRF1 gene. To address the issue of the prevalence of the most frequently observed PRF1 mutations in the control population, the authors examined a series of 400 healthy white control subjects for the 272C>T mutation (A91V).

Results: A total of 6 different mutations were identified in 12 patients (27.3%). Eleven patients had 1 mutation whereas 1 patient was found to have 2 mutations. Of the 6 PRF1 mutations identified, 2 were novel mutations: 529C>T (resulting in R177C) and 1471G>A (resulting in D491N). The remaining 4 mutations were previously described; in particular, the 272C>T mutation (resulting in the A91V amino acid change) was found in 8 patients, whereas the 368G>A (R123H), 695G>A (R232H), and 1262T>G (F421C) mutations were all found in 1 case each. Overall, the incidence of PRF1 mutations was found to be significantly higher in patients with ALCL compared with 400 control subjects, among whom only heterozygous A91V was observed in 41 subjects (10.2%) (chi-square test, 10.9; P <.01).

Conclusions: Patients with childhood ALCL have a higher probability of being a carrier of a PRF1 mutation compared with healthy controls, suggesting a possible predisposing role.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Case-Control Studies
  • Child
  • DNA Mutational Analysis
  • Genetic Predisposition to Disease
  • Germ-Line Mutation / genetics*
  • Heterozygote
  • Humans
  • Lymphoma, Large-Cell, Anaplastic / genetics*
  • Lymphoma, Large-Cell, Anaplastic / pathology
  • Perforin
  • Pore Forming Cytotoxic Proteins / genetics*
  • Prospective Studies


  • PRF1 protein, human
  • Pore Forming Cytotoxic Proteins
  • Perforin