1,724,656 research outputs found
Abstract 3390: Clonal evolution in uveal melanoma
No full textAbstract
Introduction: Uveal melanoma is the most common primary cancer of the eye and frequently gives rise to lethal metastatic disease. Uveal melanoma can be divided into two prognostic subgroups based on gene expression profiling: class 1 (low metastatic risk) and class 2 (high metastatic risk). Uveal melanoma is also notable for a characteristic set of driver mutations that cluster into two groups. The first group consists of mutually exclusive gain-of-function mutations in members of the Gαq signaling pathway (GNAQ, GNA11, CYSLTR2 and PLCB4), which are present in almost all uveal melanomas. These mutations are not prognostic, and are thought to represent initiating events that are insufficient alone to cause full malignant transformation. The second group consists of near-mutually exclusive mutations in BAP1, SF3B1, and EIF1AX. These are thought to occur later in tumor progression and are prognostic of patient outcome. These molecular features are associated with characteristic chromosome copy number variations (CNV). The purpose of this study was to investigate the life history of primary uveal melanomas by inferring the intratumoral evolution of these genetic events.
Methods: Exome or whole genome sequencing data from 151 primary uveal melanomas were evaluated with a new bioinformatic pipeline for calling mutations and CNVs. Data from this analysis were used in downstream subclonality algorithms to determine intratumor evolutionary patterns within individual tumor samples.
Results: A Gαq mutation was found in 98.7% of tumors, which were all mutually exclusive with each other. BAP1 mutations were found in 46%, SF3B1 mutations in 23%, and EIF1AX mutations in 14% of tumors, all of which were mutually exclusive with each other except for 4 cases. We identified novel driver mutations in 20% of the remaining tumors. In most samples that contained a BAP1 or SF3B1 mutation, this driver mutation and associated CNVs were present in 100% of tumor cells. However, in 14% of cases with BAP1 mutations, 100% of tumor cells exhibited monosomy 3, but a BAP1 mutation was present in a smaller subclone, suggesting that the BAP1 mutation occurred after the loss of chromosome 3. In tumors with EIF1AX mutations, this mutation was consistently found in 100% of tumor cells, with 6p gain being found in a smaller subclone in 45% of cases, suggesting that 6p gain usually occurs after the EIF1AX mutation in this subgroup of tumors.
Conclusions: The driver mutations and associated CNVs that are characteristic of uveal melanoma occur very early in tumor evolution and are followed by the accumulation of silent passenger mutations, consistent with a punctuated evolution model in which an initial “big bang” is followed by neutral non-Darwinian evolution. These unexpected findings alter prevailing theories of uveal melanoma progression, and could have a significant impact on patient management.
Citation Format: Matthew G. Field, Hima Anbunathan, Michael A. Durante, Louie Cai, Karam Alawa, Christina L. Decatur, Stefan Kurtenbach, Anne Bowcock, J. William Harbour. Clonal evolution in uveal melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3390. doi:10.1158/1538-7445.AM2017-3390</jats:p
IBM 3390 Hard Disk Platter
No full textThe 3390 disks rotated faster than those in the previous model 3380. Faster disk rotation reduced rotational delay (ie. the time required for the correct area of the disk surface to move to the point where data could be read or written). In the 3390's initial models, the average rotational delay was reduced to 7.1 milliseconds from 8.3 milliseconds for the 3380 family
Astronomische Nachrichten, nos 3385-3390
No full textR. R. Astronomische Nachrichten, nos 3385-3390. In: Bulletin astronomique, tome 14, 1897. pp. 145-150
Complex instruction manual to measuring station HIOKI 3390
No full textTato bakalářská práce se zabývá analyzátorem výkonu Hioki 3390. Práce obsahuje nastavení, základní operace a funkce přístroje. Na konci bakalářské práce je vypracován vzorový protokol, který byl změřený pomocí HIOKI 3390.This bachelor‘s thesis deals with power analyzer HIOKI 3390. Thesis contains settings, basic operations and functions of the instrument. At the end of the thesis there is a representative protocol, which was measured with Hioki 3390.
Complex instruction manual to measuring station HIOKI 3390
No full textThis bachelor‘s thesis deals with power analyzer HIOKI 3390. Thesis contains settings, basic operations and functions of the instrument. At the end of the thesis there is a representative protocol, which was measured with Hioki 3390
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
D-3390: 1090 North Main, Logan, Utah, Otto Mehr Logan Knit Company
No full textD-3390: 1090 North Main, Logan, Utah, Otto Mehr Logan Knit Compan
- …
