Real-time genomic characterization of advanced pancreatic cancer to enable precision medicine

Clinically relevant subtypes exist for pancreatic ductal adenocarcinoma (PDAC), but molecular characterization is not yet standard in clinical care. We implemented a biopsy protocol to perform time-sensitive whole-exome sequencing and RNA sequencing for patients with advanced PDAC. Therapeutically relevant genomic alterations were identified in 48% (34/71) and pathogenic/likely pathogenic germline alterations in 18% (13/71) of patients. Overall, 30% (21/71) of enrolled patients experienced a change in clinical management as a result of genomic data. Twenty-six patients had germline and/or somatic alterations in DNA-damage repair genes, and 5 additional patients had mutational signatures of homologous recombination deficiency but no identified causal genomic alteration. Two patients had oncogenic in-frame BRAF deletions, and we report the first clinical evidence that this alteration confers sensitivity to MAPK pathway inhibition. Moreover, we identified tumor/stroma gene expression signatures with clinical relevance. Collectively, these data demonstrate the feasibility and value of real-time genomic characterization of advanced PDAC.Significance: Molecular analyses of metastatic PDAC tumors are challenging due to the heterogeneous cellular composition of biopsy specimens and rapid progression of the disease. Using an integrated multidisciplinary biopsy program, we demonstrate that real-time genomic characterization of advanced PDAC can identify clinically relevant alterations that inform management of this difficult disease. Cancer Discov; 8(9); 1096-111. ©2018 AACR.See related commentary by Collisson, p. 1062This article is highlighted in the In This Issue feature, p. 1047

Role of triethanolamine and furfuraldehyde on the electrochemical deposition and dissolution- behaviour of zinc

207-212The search for the development of non-cyanide zinc plating baths resulted in identification of newer complexing ligands. The deposition and dissolution of zinc was studied by cyclic voltammetric studies using a bath composition consisted of 0.12M Zinc oxide, 2.75M sodium hydroxide and required quantity of triethanolamine and furfuraldehyde. Glassy carbon (GC), Platinum and SCE were used as working electrode, counter electrode and reference electrode respectively. The studies were made at different concentrations of the above additives at various scan rates at 30°C, The pH of the bath was maintained at 11.5 to 12.0. The deposition of zinc from zincate solutions undergoes successive reduction to zinc. The chemical step followed by first electron transfer is the slow step. Triethanolamine and furfuraldehyde were found to participate in the electron transfer process. Detailed mechanism of deposition and dissolution in presence of triethanolamine and furfuraldehyde are discussed