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Acute myeloid leukaemias (AML) arising in irradiated CBA/H mice frequently have breakpoints in the F region of chromosome 2. The closely linked cytokine genes interleukin (IL)-1 alpha and beta map to this region, and the beta gene is deregulated in some AMLs. Using pulsed-field gel electrophoresis techniques, we show here that an 800 kb 2F region encoding IL-1 alpha and beta is not obviously rearranged in six leukaemias carrying chromosome 2 abnormalities. However, changes in IL-1 region DNA methylation in three leukaemias may be consistent with loss of hypermethylated sequences from one chromosome copy. These possible 2F region losses are discussed in relation to genomic imprinting and its potential role in murine myeloid leukaemogenesis.

The murine IL-1 alpha and IL-1 beta genes encode structurally and evolutionarily related cytokines that exert a regulatory role in numerous physiological processes including hemopoiesis. Previous studies have shown these genes to be closely linked in the F region of mouse chromosome 2. Here we show, using pulsed-field gel electrophoresis, that the IL-1 alpha and beta genes of the CBA/H mouse are very closely linked and contained within a SmaI genomic fragment of approximately 70 kb. From conventional and PFGE analyses we suggest that IL-1 beta lies 5' to IL-1 alpha and that the two genes are in the same orientation and separated by approximately 50 kb. The apparent clustering of such hemopoietic genes is discussed in relation to evolutionary tandem gene duplication and possible associations with chromosomal fragile sites and leukemogenesis.

Beckwith‐Wiedemann Spectrum (BWSp) is an overgrowth and cancer predisposition disorder characterized by a wide spectrum of phenotypic manifestations including macroglossia, abdominal wall defects, neonatal hypoglycemia, and predisposition to embryonal tumors. In 1981, Best and Hoekstra reported four patients with BWSp in a single family which suggested autosomal dominant inheritance, but standard clinical testing for BWSp was not available during this time. Meticulous phenotyping of this family has occurred over the past 40 years of follow‐up with additional family members being identified and samples collected for genetic testing. Genetic testing revealed a pathogenic mutation in CDKN1C, consistent with the most common cause of familial BWSp. CDKN1C mutations account for just 5% of sporadic cases of BWSp. Here, we report the variable presentation of BWSp across the individuals affected by the CDKN1C mutation and other extended family members spanning multiple generations, all examined by the same physician. Additional phenotypes thought to be atypical in patients with BWSp were reported which included cardiac abnormalities. The incidence of tumors was documented in extended family members and included rhabdomyosarcoma, astrocytoma, and thyroid carcinoma, which have previously been reported in patients with BWSp. These observations suggest that in addition to the inheritance of the CDKN1C variant, there are modifying factors in this family driving the phenotypic spectrum observed. Alternative theories are suggested to explain the etiology of clinical variability including diffused mosaicism, anticipation, and the presence of additional variants tracking in the family. This study highlights the necessity of long‐term follow‐up in patients with BWSp and consideration of individual familial characteristics in the context of phenotype and/or (epi)genotype associations.

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