Mutational evolution in a lobular breast tumour profiled at single nucleotide resolution
NATURE
Authors: Shah, Sohrab P.; Morin, Ryan D.; Khattra, Jaswinder; Prentice, Leah; Pugh, Trevor; Burleigh, Angela; Delaney, Allen; Gelmon, Karen; Guliany, Ryan; Senz, Janine; Steidl, Christian; Holt, Robert A.; Jones, Steven; Sun, Mark; Leung, Gillian; Moore, Richard; Severson, Tesa; Taylor, Greg A.; Teschendorff, Andrew E.; Tse, Kane; Turashvili, Gulisa; Varhol, Richard; Warren, Rene L.; Watson, Peter; Zhao, Yongjun; Caldas, Carlos; Huntsman, David; Hirst, Martin; Marra, Marco A.; Aparicio, Samuel
Abstract
Recent advances in next generation sequencing(1-4) have made it possible to precisely characterize all somatic coding mutations that occur during the development and progression of individual cancers. Here we used these approaches to sequence the genomes (>43-fold coverage) and transcriptomes of an oestrogen-receptor-apositive metastatic lobular breast cancer at depth. We found 32 somatic non-synonymous coding mutations present in the metastasis, and measured the frequency of these somatic mutations in DNA from the primary tumour of the same patient, which arose 9 years earlier. Five of the 32 mutations (in ABCB11, HAUS3, SLC24A4, SNX4 and PALB2) were prevalent in the DNA of the primary tumour removed at diagnosis 9 years earlier, six ( in KIF1C, USP28, MYH8, MORC1, KIAA1468 and RNASEH2A) were present at lower frequencies (1-13%), 19 were not detected in the primary tumour, and two were undetermined. The combined analysis of genome and transcriptome data revealed two new RNA-editing events that recode the amino acid sequence of SRP9 and COG3. Taken together, our data show that single nucleotide mutational heterogeneity can be a property of low or intermediate grade primary breast cancers and that significant evolution can occur with disease progression.
Synthesis and spectroscopic characterization of tin(II) and tin(IV) complexes containing 2,3,5,6-tetrakis(alpha-pyridyl)pyrazine as a bridging ligand
JOURNAL OF THE BRAZILIAN CHEMICAL SOCIETY
Authors: Bitzer, RS; Teles, WM; Abras, A; Ardisson, JD; Filgueiras, CAL
Abstract
In this work we investigated the reactivity of the nitrogen heterocyclic ligand 2,3,5,6-tetrakis(alpha-pyridyl)pyrazine, TPP, towards six tin-containing reagents, namely SnCl2, SnX4 (X = Cl or Br, SnRCl3 (R = Ph or Me), and SnPh2Cl2. The products were characterized by microanalysis (C, H, N, and Sn), IR spectroscopy (4000-200 cm(-1)), H-1, C-13 {H-1}, C-13-CP/MAS, Sn-119, and Sn-119-MAS NMR spectroscopy, as well as by Sn-119 Mossbauer spectroscopy. All reactions yielded bimetallic adducts, in which TPP behaved as a bis-bidentate bridging ligand, binding to each metallic center through two pyridine nitrogen atoms. This coordination mode is so far quite rare and, for the first time, is reported for main group metal-TPP complexes.