Paget’s disease of bone (PDB) is a common disorder with a strong genetic component characterised by focal increases in bone turnover which in some cases is caused by SQSTM1 mutations. To identify additional susceptibility genes we performed a genome wide association study in 750 PDB cases without SQSTM1 mutations and 1002 controls and identified three candidate loci for the disease which were replicated in an independent set of 500 cases and 535 controls. The strongest signal was with rs484959 on 1p13 close to the CSF1 gene (P = 5.38 × 10−24) and significant associations were also observed with rs1561570 on 10p13 within the OPTN gene (P = 6.09 × 10−13) and with rs3018362 on 18q21 close to the TNFRSF11A gene (P = 5.27 × 10−13). These studies provide new insights into the pathogenesis of PDB and identify OPTN, CSF1 and TNFRSF11A as novel candidate genes for disease susceptibility.

A common chromosomal abnormality in childhood T-cell acute leukemia is a translocation, t(10;14) (q24;qll), that together with the variant t(7;10)(q35;q24) is present in up to 7% of this tumor type. The gene adjacent to the lOq24 region is transcriptionally activated after translocation to either TCRD (14q11) or TCRB (7q35). It encodes a homeobox gene closely related to the developmentally regulated homeotic genes of flies and mammals. The coding capacity of this activated gene, designated HOXII, is undisturbed in a T-cell line carrying the translocation t(7;10)(q35;q24). Therefore, the HOXII homeobox gene seems to be involved in T-cell tumorigenesis.

Regenerative proliferation capacity and poor differentiation are histological features usually linked to poor prognosis in head and neck squamous cell carcinoma (hnSCC). However, the pathways that regulate them remain ill-characterized. Here, we show that those traits can be triggered by the RHO GTPase activator VAV2 in keratinocytes present in the skin and oral mucosa. VAV2 is also required to maintain those traits in hnSCC patient-derived cells. This function, which is both catalysis- and RHO GTPase-dependent, is mediated by c-Myc- and YAP/TAZ-dependent transcriptomal programs associated with regenerative proliferation and cell undifferentiation, respectively. High levels of VAV2 transcripts and VAV2-regulated gene signatures are both associated with poor hnSCC patient prognosis. These results unveil a druggable pathway linked to the malignancy of specific SCC subtypes.

Poor prognosis after ischemic stroke or intracerebral hemorrhage is linked to a particular polymorphism in the human gene encoding p53.