TP53 R249S mutation detected in circulating tumour DNA is associated with Prognosis of hepatocellular carcinoma patients with or without hepatectomy.

BACKGROUND AND AIMS: Somatic mutation R249S in TP53 is highly common in hepatocellular carcinoma (HCC). We aim to investigate the effects of R249S in ctDNA on the prognosis of HCC. METHODS: We analysed three cohorts including 895 HCC patients. TP53 mutation spectrum was examined by direct sequencing of genomic DNA from tissue specimens in HCC patients with hepatectomy (Cohort 1, N = 260). R249S and other recurrent missense mutations were assessed for their biological functions and associations with overall survival (OS) and progression-free survival (PFS) of HCC patients in Cohort 1. R249S within circulating tumour DNA (ctDNA) was detected through droplet digital polymerase chain reaction (ddPCR) and its association with OS and PRS was analysed in HCC patients with (Cohort 2, N = 275) or without (Cohort 3, N = 360) hepatectomy. RESULTS: In Cohort 1, R249S occupied 60.28% of all TP53 mutations. Overexpression of R249S induced more serious malignant phenotypes than those of the other three identified TP53 recurrent missense mutations. Additionally, R249S, but not other missense mutations, was significantly associated with worse OS (P = .006) and PFS (P = .01) of HCC patients. Consistent with the results in Cohort 1, HCC patients in Cohorts 2 and 3 with R249S had worse OS (P = 8.291 × 10-7 and 2.608 × 10-7 in Cohorts 2 and 3, respectively) and PFS (P = 5.115 × 10-7 and 5.900 × 10-13 in Cohorts 2 and 3, respectively) compared to those without this mutation. CONCLUSIONS: TP53 R249S mutation in ctDNA may serve as a promising prognosis biomarker for HCC patients with or without hepatectomy.

Poly[[µ-1,4-bis-(imidazol-1-ylmeth-yl)benzene]bis-(µ(4)-cyclo-hexane-1,4-dicarboxyl-ato)dinickel(II)].

The structure of the polymeric title compound, [Ni(2)(C(8)H(10)O(4))(2)(C(14)H(14)N(4))](n), features a five-coordinate Ni(II) centre defined by four carboxyl-ate O atoms from two different cyclo-hexane-1,4-dicarboxyl-ate (chdc) ligands and an N atom from one end of a 1,4-bis-(imidazol-1-ylmeth-yl)benzene (1,4-bix) mol-ecule. The NO(4) coordination geometry is distorted square-pyramidal with the N atom in the apical position. Each end of the chdc ligand links pairs of Ni(II) atoms into a paddle-wheel assembly, i.e. Ni(2)(O(2)CR')(4). These are connected into rows owing to the bridging nature of the chdc ligands, and the rows are connected into a two-dimensional grid via the 1,4-bix ligands. The 1,4-bix ligand, which is disposed about a centre of inversion, is disorderd. Two positions of equal occupancy were discerned for the -H(2)C(C(6)H(4))CH(2)- residue.