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Childhood T-cell non-Hodgkin's lymphoma, colorectal carcinoma and brain tumor in association with café-au-lait spots caused by a novel homozygous PMS2 mutation

Leukemia volume 22, pages 1078–1080 (2008)Cite this article

Heterozygous germline loss-of-function mutations of the genes encoding the crucial components of this MMR system, MLH1, MSH2, MSH6 or PMS2, cause Lynch syndrome, a well-characterized dominant cancer syndrome associated with hereditary non-polyposis colorectal cancer, and other malignancies (reviewed in Peltomaki3). Tumors arising in these individuals result from somatic loss of the remaining wild type MLH1, MSH2, MSH6 or PMS2 allele, which leads to impaired MMR and accumulation of somatic mutations.

In contrast to individuals with Lynch syndrome who harbor a heterozygous mutant MMR gene allele, rare cases with biallelic germline mutations have been reported. Biallelic mutations of MLH1, MSH2, MSH6 or PMS2 cause a recessive childhood cancer syndrome characterized by café-au-lait spots and other signs of neurofibromatosis type 1, childhood brain tumors, leukemia, lymphoma, colorectal cancer and other malignancies (reviewed in Felton et al.4). This syndrome is referred to as childhood cancer syndrome,5 mismatch repair deficiency (MMR-D) syndrome6 or Lynch III syndrome.7 To date, 14 families with a biallelic PMS2 lesion have been described,5, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 and PMS2 deficient mice have been shown to be at high tumor (mainly lymphoma) risk.18

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Authors and Affiliations

  1. Division of Pediatric Hematology/Oncology, Department of Pediatrics and Adolescent Medicine, University of Freiburg, Freiburg, Germany

    C P Kratz, C M Niemeyer, M Kartal, U Kontny & M Lauten

  2. Department of Pathology, University of Freiburg, Freiburg, Germany

    E Jüttner & A Schmitt-Graeff

  3. Department of Medical Genetics, Medical University of Vienna, Vienna, Austria

    A Weninger, C Fonatsch & K Wimmer

  4. Department of Surgery, University of Freiburg, Freiburg, Germany

    S Utzolino & J Rädecke

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  1. C P Kratz
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Correspondence to C P Kratz.

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Kratz, C., Niemeyer, C., Jüttner, E. et al. Childhood T-cell non-Hodgkin's lymphoma, colorectal carcinoma and brain tumor in association with café-au-lait spots caused by a novel homozygous PMS2 mutation. Leukemia 22, 1078–1080 (2008). https://doi.org/10.1038/sj.leu.2405008

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