Key Points Myeloid cells in subjects with cancer contain fibrocytes, a cell subset previously implicated in chronic inflammation. Fibrocytes in cancer patients are immunosuppressive and may contribute to immune escape.

Background:Uveal melanoma is the most frequent primary tumour of the eye. It is molecularly clearly distinct from cutaneous melanoma and shows a different pattern of driver mutations. The influence of sunlight ultraviolet (UV) exposure on the aetiology of uveal melanoma is a matter of debate. The recent identification of driver mutations in the promoter of the telomerase reverse transcriptase (TERT) gene with UV-induced cytidine-to-thymidine transitions in cutaneous melanoma prompted us to investigate whether these mutations also occur in uveal melanoma.Methods:We analysed 50 cases of uveal melanoma obtained from enucleation surgery for mutations in the genes GNAQ, GNA11, BAP1, SF3B1, EIFAX1 and TERT, measured gene expression using microarrays and analysed gene copy numbers by SNP arrays.Results:We detected a TERT mutation in only one case of a 57-year-old white male patient with clinical and histopathological features typical for uveal melanoma. The tumour showed mutations in GNA11 and EIF1AX that are typical for uveal melanoma and absent from cutaneous melanoma. No mutations were detected in GNAQ, BAP1 and SF3B1 that are frequently mutated in uveal melanoma. Both copies of chromosome 3 were retained. Several tumours among which the one carrying the TERT promoter mutation showed elevated TERT expression. Consistent with previous reports, GNAQ is inversely associated with chromosome 3 monosomy and metastasis. BAP1 mutations are significantly associated with chromosome 3 monosomy but not with relapse.Conclusion:These data indicate that TERT mutations are rare in uveal melanoma. No conclusion can be drawn on their potential influence on tumour progression.

Proliferation and programmed cell death are tightly correlated with the ubiquitin-proteasome system (UPS). Alterations in the UPS may be implicated in pathological conditions such as the proteasome over-activity in cancer cells. Mounting evidence indicates that many types of actively proliferating malignant cells are more sensitive to proteasome inhibition than normal cells, and therefore UPS inhibitors are actively pursued as anticancer agents. The approval of the proteasome inhibitor drug bortezomib for the treatment of myeloma and lymphoma further highlights the need for UPS inhibitors. Recent studies have suggested that clioquinol and 5-amino-8-hydroxyquinoline can inhibit proteasome activity and induce apoptosis in human cancer cells. As for clioquinol, a copper-dependent and -independent mechanism has been proposed to explain the inhibition of the proteasome whereas the activity of 5-amino-8-hydroxyquinoline has not been explored in the presence of copper(ii) ions. Herein, we investigated the biological activity of some 8-hydroxyquinolines by using human ovarian (A2780) and lung (A549) cancer cells. The effect of copper(ii) on the activity of these compounds was also evaluated. The investigated systems inhibit the chymotrypsin-like activity of the proteasome and induce growth inhibition and apoptosis in a concentration-dependent manner. Copper(ii) ions increase the activity of 8-hydroxyquinoline derivatives except in the case of 5-amino-8-hydroxyquinoline. This study suggests the great potential of amino- and chloro-8-hydroxyquinolines as anticancer agents. Furthermore, it clarifies some aspects concerning the activity of 5-amino-8-hydroxyquinoline, which has been previously proposed as a proteasome inhibitor capable of overcoming resistance to bortezomib.

BackgroundDifferentiated thyroid carcinoma offers a good model to investigate the possible correlation between specific gene mutations and chromosome instability. Papillary thyroid neoplasms are characterized by different mutually exclusive genetic alterations, some of which are associated with aneuploidy and aggressive phenotype.ResultsWe investigated the centrosome status and mitotic abnormalities in three thyroid carcinoma-derived cell lines, each maintaining the specific, biologically relevant gene alteration harbored by the parental tumors: RET/PTC1 rearrangement in TPC1; heterozygous and homozygous BRAFV600E mutation in K1 and in B-CPAP, respectively. B-CPAP cells showed a statistically significant (P < 0.01) higher frequency of abnormal mitotic figures compared to TPC1 and K1 cells.ConclusionsOur data indicate that RET/PTC1 oncogenic activity is not related to mitotic chromosome impairment and missegregation whereas, based on the consistent difference in types/frequencies of centrosome and spindle abnormalities observed between K1 and B-CPAP cells, the hetero/homozygous allelic status of BRAFV600E mutation seems to be not irrelevant in respect to chromosomal instability development.