Ruth Rimokh

A chromosomal translocation involving a breakpoint on the long arm of chromosome 5 at position q35 has been reported previously in 17 cases of neoplasia. In 14 of these cases the translocation involves exchange of material between chromosome 2 p23 and chromosome 5. Most cases had been diagnosed histologically as malignant histiocytosis but it was suggested recently, following the study of three cases in one of the author's laboratories, that such tumours are in reality lymphoid tumours. In the present paper we report on 12 further neoplasms with a translocation involving the 5q35 breakpoint and show that all were large cell lymphomas expressing the CD30 (Ki-1) antigen, often classifiable histologically as 'Ki-1 lymphoma'. In five cases there was evidence, based on antigen expression and/or genotypic studies, that the neoplasm was of T lymphoid derivation. These findings provide further evidence that translocations involving 5q35 are associated not with histiocytic malignancy, but with large cell lymphoid neoplasms, including typical cases of 'Ki-1 lymphoma' or 'anaplastic large cell lymphoma'. Since cell lines have been established from five of these cases it may be possible in the future to clone the breakpoint on chromosome 5 and to investigate whether there is a gene in its vicinity with oncogenic potential.

Germ-line mutations in the BRCA1 gene strongly predispose women to breast cancer (lifetime risk up to 80%). Furthermore, the BRCA1 protein is absent or present at very low levels in about one third of sporadic breast cancers. However, the mechanisms underlying BRCA1 somatic inactivation appear multiple and are still not fully understood. We report here the involvement of miR-146a and miR-146b-5p that bind to the same site in the 3'UTR of BRCA1 and down-regulate its expression as demonstrated using reporter assays. This was further confirmed with the endogenous BRCA1 gene by transfecting microRNA (miRNA) precursors or inhibitors in mammary cell lines. This down-regulation was accompanied by an increased proliferation and a reduced homologous recombination rate, two processes controlled by BRCA1. Furthermore, we showed that the highest levels of miR-146a and/or miR-146b-5p are found in basal-like mammary tumour epithelial cell lines and in triple negative breast tumours, which are the closest to tumours arising in carriers of BRCA1 mutations. This work provides further evidence for the involvement of miRNAs in sporadic breast cancer through down-regulation of BRCA1.

Two cases of non-Hodgkin's lymphoma are reported in which a chromosomal translocation was observed involving the same site (q35) on the long arm of chromosome 5. The other breakpoint involved in the translocation was chromosome 2 (p23) in one case and chromosome 3 (q12) in the other. Both cases were large cell lymphomas expressing CD30 antigen ('Ki-1 lymphoma'). One was clearly of T lymphoid origin, the other probably B cell derived. One other case of a Ki-1 lymphoma with 2;5 translocation (involving the same breakpoint on chromosome 5) has been reported previously, and it is suggested that this cytogenetic abnormality may be specifically associated with Ki-1 lymphoma. The literature contains a further eight cases of lymphoid neoplasms with a translocation involving a breakpoint at q35 on chromosome 5. They have all been described as cases of 'malignant histiocytosis', but the present findings make it likely that these cases were in reality also examples of Ki-1 lymphoma. The breakpoint at the q35 region on chromosome 5 is close to the position of the fms proto-oncogene, suggesting that an abnormality affecting this gene might possibly play a causal role in 'Ki-1 lymphoma'. However, DNA restriction fragment analysis of the present cases showed no evidence that the breakpoint on chromosome 5 involves the fms gene or its immediate vicinity.