Toshikatsu Fukuda

Mutations of a novel human RAD54 homologue, RAD54B , in primary cancer

Association of breast tumor susceptibility gene products BRCA1 and BRCA2 with the RAD51 recombination protein suggested that cancer could arise through defects in recombination. The identification of NBS1, responsible for Nijmegen breakage syndrome, from the MRE11/RAD50 recombination protein complex also supports this hypothesis. However, our mutation analysis revealed that known members of the RAD52 epistasis group are rarely mutated in human primary cancer. Here we describe the isolation of a novel member of the SNF2 superfamily, characterized with sequence motifs similar to those in DNA and RNA helicases. The gene, designated RAD54B, is significantly homologous to the RAD54 recombination gene. The expression of RAD54B was high in testis and spleen, which are active in meiotic and mitotic recombination. These findings suggest that RAD54B may play an active role in recombination processes in concert with other members of the RAD52 epistasis group. RAD54B maps to human chromosome 8q21.3-q22 in a region associated with cancer-related chromosomal abnormalities. Homozygous mutations at highly conserved positions of RAD54B were observed in human primary lymphoma and colon cancer. These findings suggest that some cancers arise through alterations of the RAD54B function.

Mutations in the RAD54 recombination gene in primary cancers

Association of a recombinational repair protein RAD51 with tumor suppressors BRCA1 and BRCA2 suggests that defects in homologous recombination are responsible for tumor formation. Also recent findings that a protein associated with the MRE11/RAD50 repair complex is mutated in Nijmegen breakage syndrome characterized by increased cancer incidence and ionizing radiation sensitivity strongly support this idea. However, the direct roles of BRCA proteins and the protein responsible for NBS in recombinational repair are not clear though they are associated with the recombinational repair complexes. Since RAD51 forms a complex with other members of the RAD52 epistasis group and with BRCA proteins, it is reasonable to ask if alterations of members of the RAD52 epistasis group lead to tumor development. Here we describe missense mutations at functional regions of RAD54 and the absence of the wild-type RAD54 expression resulting from aberrant splicing in primary cancers. Since RAD54 is a recombinational protein associated with RAD51, this is the first genetic evidence that cancer arises from a defect in repair processes involving homologous recombination.

Ruptured Superior Mesenteric Artery Aneurysm Occurring in Association with a Heterotopic Pancreas: Report of a Case

Aneurysmal disease of the visceral arteries is found in only about 0.2% of the population, and the celiac trunk and superior mesenteric artery (SMA) are involved in less than 10% of all visceral aneurysms. We present herein the case of a 71-year-old woman who suffered rupture of a SMA aneurysm. Histological examination of the periarterial tissues which existed next to the aneurysm revealed a heterotopic pancreas. To the best of our knowledge, no other case of an SMA branch aneurysm presenting in association with a heterotopic pancreas has ever been described in either the Japanese or English literature. This is the first report to indicate that a heterotopic pancreas is a likely incidental factor predisposing to visceral aneurysms.