Key Points PS can be overlooked in the differential diagnosis of children with severe congenital anemia. mtDNA deletion testing should be included in the genetic evaluation of patients with congenital anemia of unclear etiology.

Nijmegen breakage syndrome (NBS) is a human autosomal recessive disease characterized by genomic instability and enhanced cancer predisposition, in particular to lymphoma and leukemia. Recently, significantly higher frequencies of heterozygous carriers of the Slavic founder NBS1 mutation, 657del5, were found in Russian children with sporadic lymphoid malignancies, and in Polish adults with non-Hodgkin lymphoma (NHL). In addition, the substitution 643C>T (R215W) has also been found in excess among children with acute lymphoblastic leukemia (ALL). In an attempt to asses the contribution of both mutations to the development of sporadic lymphoid malignancies, we analyzed DNA samples from a large group of Polish pediatric patients. The NBS1 mutation 657del5 on one allele was found in 3 of 270 patients with ALL and 2 of 212 children and adolescents with NHL; no carrier was found among 63 patients with Hodgkin lymphoma (HL). No carriers of the variant R215W were detected in any studied group. The relative frequency of the 657del5 mutation was calculated from a total of 6,984 controls matched by place of patient residence, of whom 42 were found to be carriers (frequency 5 0.006). In the analyzed population with malignancies, an increased odds ratio for the occurrence of mutation 657del5 was found in comparison with the control Polish population (OR range 1.48-1.85, 95% confidence interval 1.18-2.65). This finding indicates that the frequency of the mutation carriers was indeed increased in patients with ALL and NHL (p < 0.05). Nonetheless, NBS1 gene heterozygosity is not a major risk factor for lymphoid malignancies in childhood and adolescence. ' 2005 Wiley-Liss, Inc.Key words: lymphoid tissue malignancies; childhood and adolescence; NBS1 gene; 657del5 mutation; Nijmegen breakage syndrome Nijmegen breakage syndrome (NBS) (OMIM *251260) is a human autosomal recessive disease characterized by microcephaly, immunodeficiency, hypersensitivity to ionizing radiation and a very high incidence of cancer, particularly of lymphoid origin.1,2 The disease seems to be more prevalent among Central and Eastern European populations, with Polish patients constituting approximately half of all registered NBS patients worldwide. The great majority of NBS patients (>90%) share a pathogenic truncating mutation, 657del5, within exon 6 of the NBS1 gene. 3The NBS1 gene encodes a protein called nibrin or p95NBS1, which forms a multimeric complex with hMRE11 and hRAD50 (N/M/R complex) involved in recombination repair of DNA double-strand breaks (DNA DSBs) in yeast and mammals.3,4 DNA DSBs occur as intermediates in physiological events, such as V(D)J recombination during early B and T cell development and immunoglobulin (Ig) class switch in mature B cells, but most frequently are generated by mutagenic agents such as ionizing radiation and radio-mimetic chemicals. DNA DSBs represent the most serious DNA damage, which, if not repaired accurately, can result in genomic instability, including chromosome rearrangements or gene mutations, and finally...

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Anaplastic lymphoma kinase (ALK) positive diffuse large B-cell lymphoma (DLBCL) is a rare subtype of non-Hodgkins lymphoma. Five such cases have been described in children. We present a 9-year-old boy, in whom diagnosis of DLBCL has been established in addition to congenital multiple enchondromatosis. Immunohistopathological evaluation of tumor biopsy established the final diagnosis of ALK + DLBCL. The clathrin gene (CLTC)-ALK fusion underlying aberrant expression of ALK in the present case was demonstrated by interphase fluorescence in situ hybridization (FISH) using break-apart rearrangement probes for ALK and CLTC. The disease in this patient was highly resistant to applied chemotherapy regimens and to radiotherapy. Analysis of the disease course in our patient and review of other cases reported previously show that ALK + DLBCL can be an aggressive malignancy that can be cured with conventional chemotherapy protocols only at stage of localized disease.