No abstract

When in a patient more than one tumour in the same or a different organ is diagnosed, multiple primary tumours may be present. For epidemiological studies, different definitions of multiple primaries are used with the two main definitions coming from the project Surveillance Epidemiology and End Results and the International Association of Cancer Registries and International Agency for Research on Cancer. The differences in the two definitions have to be taken into consideration when reports on multiple primaries are analysed. In this review, the literature on multiple primaries is reviewed and summarised. Overall, the frequency of multiple primaries is reported in the range of 2–17%.Aetiological factors that may predispose patients to multiple primaries can be grouped into host related, lifestyle factors and environmental influences. Some of the most common cancer predisposition syndromes based on a clinical presentation are discussed and the relevant genetic evaluation and testing are characterised.Importantly, from a clinical standpoint, clinical situations when multiple primaries should be suspected and ruled out in a patient are discussed.Furthermore, general principles and possible treatment strategies for patients with synchronous and metachronous multiple primary tumours are highlighted.

In conclusion, the efficacy of immunotherapy is dependent on the metastatic location. Treatment appears more active in lymph nodes compared to other organ sites such as liver, adrenals and bone. Future strategies may include additional local treatment in case of oligoprogression in these organs in patients with otherwise sustained treatment benefit.

BACKGROUND: CCAAT/enhancer-binding protein-a (CEBPA) is crucial for normal granulopoiesis and is frequently disrupted in acute myeloid leukaemia (AML). Increasing evidence suggests that CEBPA exerts its effects, in parts, by regulating specific microRNAs (miRNAs), as previously shown for miR-223. The aim of this study was to investigate the genome-wide pattern of miRNAs regulated by CEBPA in myeloid cells. METHODS: In Kasumi-1 cells, conditionally expressing CEBPA, we assessed the expression of 470 human miRNAs by microarray analysis. We further investigated the microarray results by qRT-PCR, luciferase reporter assays, and chromatin immunoprecipitation assays. RESULTS: In all, 18 miRNAs were more than two-fold suppressed or induced after CEBPA restoration. Among these 18 miRNAs, we focused on CEBPA-mediated regulation of the tumour-suppressive miR-29b. We observed that miR-29b is suppressed in AML patients with impaired CEBPA function or loss of chromosome 7q. We found that CEBPA selectively regulates miR-29b expression on its miR-29a/b1 locus on chromosome 7q32.3, whereas miR-29b2/c on chromosome 1q32.2 is not affected. CONCLUSION: This study reports the activation of the tumour-suppressive miR-29b by the haematopoietic key transcription factor CEBPA. Our data provide a rationale for miR-29b suppression in AML patients with loss of chromosome 7q or CEBPA deficiency.