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https://www.readbyqxmd.com/read/28110020/tumor-evolution-linear-branching-neutral-or-punctuated
#1
Alexander Davis, Ruli Gao, Nicholas Navin
Intratumor heterogeneity has been widely reported in human cancers, but our knowledge of how this genetic diversity emerges over time remains limited. A central challenge in studying tumor evolution is the difficulty in collecting longitudinal samples from cancer patients. Consequently, most studies have inferred tumor evolution from single time-point samples, providing very indirect information. These data have led to several competing models of tumor evolution: linear, branching, neutral and punctuated. Each model makes different assumptions regarding the timing of mutations and selection of clones, and therefore has different implications for the diagnosis and therapeutic treatment of cancer patients...
January 18, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28103823/stepwise-addition-of-genetic-changes-correlated-with-histological-change-from-well-differentiated-to-sarcomatoid-phenotypes-a-case-report
#2
Taichiro Goto, Yosuke Hirotsu, Hitoshi Mochizuki, Takahiro Nakagomi, Toshio Oyama, Kenji Amemiya, Masao Omata
BACKGROUND: Sarcomatoid cancer is defined by the World Health Organization as a category of non-small cell lung cancers with sarcoma or sarcoma-like differentiation. They are characterized by poor prognosis and resistance to conventional chemotherapy. However, the mutational profile of sarcomatoid cancer remains yet to be elucidated. Sarcomatoid cancers are usually biphasic tumors composed of carcinomatous and sarcomatous components, but the evolutional development of sarcomatoid cancer is controversial...
January 19, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28101733/3d-absorbed-dose-distribution-estimated-by-monte-carlo-simulation-in-radionuclide-therapy-with-a-monoclonal-antibody-targeting-synovial-sarcoma
#3
David Sarrut, Jean-Noël Badel, Adrien Halty, Gwenaelle Garin, David Perol, Philippe Cassier, Jean-Yves Blay, David Kryza, Anne-Laure Giraudet
BACKROUND: Radiolabeled OTSA101, a monoclonal antibody targeting synovial sarcoma (SS) developed by OncoTherapy Science, was used to treat relapsing SS metastases following a theranostic procedure: in case of significant (111)In-OTSA101 tumor uptake and favorable biodistribution, patient was randomly treated with 370/1110 MBq (90)Y-OTSA101. Monte Carlo-based 3D dosimetry integrating time-activity curves in VOI was performed on (111)In-OTSA101 repeated SPECT/CT. Estimated absorbed doses (AD) in normal tissues were compared to biological side effects and to the admitted maximal tolerated absorbed dose (MTD) in normal organs...
December 2017: EJNMMI Physics
https://www.readbyqxmd.com/read/28099366/does-the-distribution-pattern-of-brain-metastases-during-braf-inhibitor-therapy-reflect-phenotype-switching
#4
Silvia A Haueis, Pascale Kränzlin, Joanna Mangana, Phil F Cheng, Mirjana Urosevic-Maiwald, Ralph P Braun, Mitchell P Levesque, Reinhard Dummer, Simone M Goldinger
Brain metastases (brain mets) are frequent in metastatic melanoma patients. The aim of this study was to investigate the morphology and progression pattern of brain mets in melanoma patients treated with BRAF inhibitors (BRAFi) compared with patients who did not receive targeted therapy (BRAFi group and control group). The number and size of brain mets were compared between a baseline and a comparative MRI at progression. The number of brain mets was grouped into seven number classes (N=1-4, N=5-10, N=11-20, N=21-30, N=31-40, N=41-50, and N>50) and its difference was reported as the change of class that occurred...
January 17, 2017: Melanoma Research
https://www.readbyqxmd.com/read/28097046/molecular-classification-of-tissue-from-a-transformed-non-hogkin-s-lymphoma-case-with-unexpected-long-time-remission
#5
Julie Støve Bødker, Marianne Tang Severinsen, Tarec Christoffer El-Galaly, Rasmus Froberg Brøndum, Maria Bach Laursen, Steffen Falgreen, Mette Nyegaard, Alexander Schmitz, Lasse Hjort Jakobsen, Anna Amanda Schönherz, Hanne Due, Linn Reinholdt, Martin Bøgsted, Karen Dybkær, Hans Erik Johnsen
BACKGROUND: The concept of precision medicine in cancer includes individual molecular studies to predict clinical outcomes. In the present N = 1 case we retrospectively have analysed lymphoma tissue by exome sequencing and global gene expression in a patient with unexpected long-term remission following relaps. The goals were to phenotype the diagnostic and relapsed lymphoma tissue and evaluate its pattern. Furthermore, to identify mutations available for targeted therapy and expression of genes to predict specific drug effects by resistance gene signatures (REGS) for R-CHOP as described at http://www...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/28096247/order-matters-the-order-of-somatic-mutations-influences-cancer-evolution
#6
David G Kent, Anthony R Green
Cancers evolve as a consequence of multiple somatic lesions, with competition between subclones and sequential subclonal evolution. Some driver mutations arise either early or late in the evolution of different individual tumors, suggesting that the final malignant properties of a subclone reflect the sum of mutations acquired rather than the order in which they arose. However, very little is known about the cellular consequences of altering the order in which mutations are acquired. Recent studies of human myeloproliferative neoplasms show that the order in which individual mutations are acquired has a dramatic impact on the cell biological and molecular properties of tumor-initiating cells...
January 17, 2017: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/28096240/coevolution-of-leukemia-and-host-immune-cells-in-chronic-lymphocytic-leukemia
#7
Noelia Purroy, C J Wu
Cumulative studies on the dissection of changes in driver genetic lesions in cancer across the course of the disease have provided powerful insights into the adaptive mechanisms of tumors in response to the selective pressures of therapy and environmental changes. In particular, the advent of next-generation-sequencing (NGS)-based technologies and its implementation for the large-scale comprehensive analyses of cancers have greatly advanced our understanding of cancer as a complex dynamic system wherein genetically distinct subclones interact and compete during tumor evolution...
January 17, 2017: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/28096087/diffuse-large-b-cell-lymphoma-genotyping-on-the-liquid-biopsy
#8
Davide Rossi, Fary Diop, Elisa Spaccarotella, Sara Monti, Manuela Zanni, Silvia Rasi, Clara Deambrogi, Valeria Spina, Alessio Bruscaggin, Chiara Favini, Roberto Serra, Antonio Ramponi, Renzo Boldorini, Robin Foa', Gianluca Gaidano
Accessible and real-time genotyping for diagnostic, prognostic or treatment purposes is increasingly impelling in diffuse large B-cell lymphoma (DLBCL). Cell-free DNA (cfDNA) is shed into the blood by tumor cells undergoing apoptosis and can be used as source of tumor DNA for the identification of DLBCL mutations, clonal evolution, and genetic mechanisms of resistance. Here we aimed at tracking the basal DLBCL genetic profile and its modification upon treatment using plasma cfDNA. Ultra-deep targeted next generation sequencing of pre-treatment plasma cfDNA from DLBCL patients correctly discovered DLBCL-associated mutations that were represented in >20% of the alleles of the tumor biopsy with a >90% sensitivity and a ~100% specificity...
January 17, 2017: Blood
https://www.readbyqxmd.com/read/28095866/improvement-of-displacement-estimation-of-breast-tissue-in-ultrasound-elastography-using-the-monogenic-signal
#9
Taher Slimi, Ines Marzouk Moussa, Tarek Kraiem, Halima Mahjoubi
BACKGROUND: In breast ultrasound elastography, tissues displacements estimation is obtained through a technique that follows the evolution of tissues under stress. However, during the acquisition of B-mode images, tissue displacements are often contaminated with multiplicative noise caused by changes in the speckle pattern in the tissue. Thus, the application of monogenic signal technique on the B-mode image in order to estimate displacement tissue, result in a presence of amplified noise in the deformation tissue image, which severely obscures the useful information...
January 17, 2017: Biomedical Engineering Online
https://www.readbyqxmd.com/read/28094848/the-eighth-edition-ajcc-cancer-staging-manual-continuing-to-build-a-bridge-from-a-population-based-to-a-more-personalized-approach-to-cancer-staging
#10
Mahul B Amin, Frederick L Greene, Stephen B Edge, Carolyn C Compton, Jeffrey E Gershenwald, Robert K Brookland, Laura Meyer, Donna M Gress, David R Byrd, David P Winchester
The American Joint Committee on Cancer (AJCC) staging manual has become the benchmark for classifying patients with cancer, defining prognosis, and determining the best treatment approaches. Many view the primary role of the tumor, lymph node, metastasis (TNM) system as that of a standardized classification system for evaluating cancer at a population level in terms of the extent of disease, both at initial presentation and after surgical treatment, and the overall impact of improvements in cancer treatment...
January 17, 2017: CA: a Cancer Journal for Clinicians
https://www.readbyqxmd.com/read/28093659/clinical-and-molecular-relevance-of-mutant-allele-tumor-heterogeneity-in-breast-cancer
#11
Ding Ma, Yi-Zhou Jiang, Xi-Yu Liu, Yi-Rong Liu, Zhi-Ming Shao
PURPOSE: Intra-tumor heterogeneity (ITH) plays a pivotal role in driving breast cancer progression and therapeutic resistance. We used a mutant-allele tumor heterogeneity (MATH) algorithm to measure ITH and explored its correlation with clinical parameters and multi-omics data. METHODS: We assessed 916 female breast cancer patients from The Cancer Genome Atlas. We calculated the MATH values from whole-exome sequencing data and further investigated their correlation with clinical characteristics, somatic mutations, somatic copy number alterations (SCNAs), and gene enrichment...
January 16, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28092686/epigenomic-reprogramming-during-pancreatic-cancer-progression-links-anabolic-glucose-metabolism-to-distant-metastasis
#12
Oliver G McDonald, Xin Li, Tyler Saunders, Rakel Tryggvadottir, Samantha J Mentch, Marc O Warmoes, Anna E Word, Alessandro Carrer, Tal H Salz, Sonoko Natsume, Kimberly M Stauffer, Alvin Makohon-Moore, Yi Zhong, Hao Wu, Kathryn E Wellen, Jason W Locasale, Christine A Iacobuzio-Donahue, Andrew P Feinberg
During the progression of pancreatic ductal adenocarcinoma (PDAC), heterogeneous subclonal populations emerge that drive primary tumor growth, regional spread, distant metastasis, and patient death. However, the genetics of metastases largely reflects that of the primary tumor in untreated patients, and PDAC driver mutations are shared by all subclones. This raises the possibility that an epigenetic process might operate during metastasis. Here we report large-scale reprogramming of chromatin modifications during the natural evolution of distant metastasis...
January 16, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28092370/api5-confers-cancer-stem-cell-like-properties-through-the-fgf2-nanog-axis
#13
K-H Song, H Cho, S Kim, H-J Lee, S J Oh, S R Woo, S-O Hong, H S Jang, K H Noh, C H Choi, J-Y Chung, S M Hewitt, J-H Kim, M Son, S-H Kim, B I Lee, H-C Park, Y-K Bae, T W Kim
Immune selection drives the evolution of tumor cells toward an immune-resistant and cancer stem cell (CSC)-like phenotype. We reported that apoptosis inhibitor-5 (API5) acts as an immune escape factor, which has a significant role in controlling immune resistance to antigen-specific T cells, but its functional association with CSC-like properties remains largely unknown. In this study, we demonstrated for the first time that API5 confers CSC-like properties, including NANOG expression, the frequency of CD44-positive cells and sphere-forming capacity...
January 16, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28092266/tgf-%C3%AE-reduces-dna-ds-break-repair-mechanisms-to-heighten-genetic-diversity-and-adaptability-of-cd44-cd24-cancer-cells
#14
Debjani Pal, Anja Pertot, Nitin H Shirole, Zhan Yao, Naishitha Anaparthy, Tyler Garvin, Hilary Cox, Kenneth Chang, Fred Rollins, Jude Kendall, Leyla Edwards, Vijay A Singh, Gary C Stone, Michael C Schatz, James Hicks, Gregory Hannon, Raffaella Sordella
Many lines of evidence have indicated that both genetic and non-genetic determinants can contribute to intra-tumor heterogeneity and influence cancer outcomes. Among the best described sub-population of cancer cells generated by non-genetic mechanisms are cells characterized by a CD44+/CD24- cell surface marker profile. Here, we report that human CD44+/CD24- cancer cells are genetically highly unstable due to intrinsic defects in their DNA repair capabilities. In fact, in CD44+/CD24- cells constitutive activation of the TGF-beta axis was both necessary and sufficient to reduce the expression of genes that are critical in coordinating DNA damage repair mechanisms...
January 16, 2017: ELife
https://www.readbyqxmd.com/read/28092256/-resection-of-intracardiac-myxoma-case-report
#15
Víctor Manuel Carmona-Delgado, Angélica María Deloya-Maldonado, María Lourdes Carranza-Bernal, Arturo Hinojosa-Pérez, Leobardo Farías-Mayene
Myxomas are the most common benign cardiac tumors, which are considered emergency surgery. The resection should not be delayed because 8-9% of affected patients may die due to intracardiac blood flow obstruction. We presente a clinical case of a 47 year old female, history of dyslipidemia. Disease starts with retrosternal oppression feeling, dyspnea on moderate exercise, dizziness, pain in joints hands. Arrhytmic heart sounds, diastolic mitral murmur II/IV, breth sounds present, no lymph. Laboratory: hemoglobin 11...
January 2017: Revista Médica del Instituto Mexicano del Seguro Social
https://www.readbyqxmd.com/read/28090586/holliday-junction-trap-shows-how-cells-use-recombination-and-a-junction-guardian-role-of-recq-helicase
#16
Jun Xia, Li-Tzu Chen, Qian Mei, Chien-Hui Ma, Jennifer A Halliday, Hsin-Yu Lin, David Magnan, John P Pribis, Devon M Fitzgerald, Holly M Hamilton, Megan Richters, Ralf B Nehring, Xi Shen, Lei Li, David Bates, P J Hastings, Christophe Herman, Makkuni Jayaram, Susan M Rosenberg
DNA repair by homologous recombination (HR) underpins cell survival and fuels genome instability, cancer, and evolution. However, the main kinds and sources of DNA damage repaired by HR in somatic cells and the roles of important HR proteins remain elusive. We present engineered proteins that trap, map, and quantify Holliday junctions (HJs), a central DNA intermediate in HR, based on catalytically deficient mutant RuvC protein of Escherichia coli. We use RuvCDefGFP (RDG) to map genomic footprints of HR at defined DNA breaks in E...
November 2016: Science Advances
https://www.readbyqxmd.com/read/28087256/manganese-superoxide-dismutase-and-glutathione-peroxidase-1-contribute-to-the-rise-and-fall-of-mitochondrial-reactive-oxygen-species-which-drive-oncogenesis
#17
REVIEW
Dede N Ekoue, Chenxia He, Alan M Diamond, Marcelo G Bonini
Reactive oxygen species (ROS) largely originating in the mitochondria play essential roles in the metabolic and (epi)genetic reprogramming of cancer cell evolution towards more aggressive phenotypes. Recent studies have indicated that the activity of superoxide dismutase (SOD2) may promote tumor progression by serving as a source of hydrogen peroxide (H2O2). H2O2 is a form of ROS that is particularly active as a redox agent affecting cell signaling due to its ability to freely diffuse out of the mitochondria and alter redox active amino acid residues on regulatory proteins...
January 10, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28079877/genome-wide-transposon-screening-and-quantitative-insertion-site-sequencing-for-cancer-gene-discovery-in-mice
#18
Mathias J Friedrich, Lena Rad, Iraad F Bronner, Alexander Strong, Wei Wang, Julia Weber, Matthew Mayho, Hannes Ponstingl, Thomas Engleitner, Carolyn Grove, Anja Pfaus, Dieter Saur, Juan Cadiñanos, Michael A Quail, George S Vassiliou, Pentao Liu, Allan Bradley, Roland Rad
Transposon-mediated forward genetics screening in mice has emerged as a powerful tool for cancer gene discovery. It pinpoints cancer drivers that are difficult to find with other approaches, thus complementing the sequencing-based census of human cancer genes. We describe here a large series of mouse lines for insertional mutagenesis that are compatible with two transposon systems, PiggyBac and Sleeping Beauty, and give guidance on the use of different engineered transposon variants for constitutive or tissue-specific cancer gene discovery screening...
February 2017: Nature Protocols
https://www.readbyqxmd.com/read/28076811/modeling-the-effect-of-curvature-on-the-collective-behavior-of-cells-growing-new-tissue
#19
Mohd Almie Alias, Pascal R Buenzli
The growth of several biological tissues is known to be controlled in part by local geometrical features, such as the curvature of the tissue interface. This control leads to changes in tissue shape that in turn can affect the tissue's evolution. Understanding the cellular basis of this control is highly significant for bioscaffold tissue engineering, the evolution of bone microarchitecture, wound healing, and tumor growth. Although previous models have proposed geometrical relationships between tissue growth and curvature, the role of cell density and cell vigor remains poorly understood...
January 10, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28073006/bcl9l-dysfunction-impairs-caspase-2-expression-permitting-aneuploidy-tolerance-in-colorectal-cancer
#20
Carlos López-García, Laurent Sansregret, Enric Domingo, Nicholas McGranahan, Sebastijan Hobor, Nicolai Juul Birkbak, Stuart Horswell, Eva Grönroos, Francesco Favero, Andrew J Rowan, Nicholas Matthews, Sharmin Begum, Benjamin Phillimore, Rebecca Burrell, Dahmane Oukrif, Bradley Spencer-Dene, Michal Kovac, Gordon Stamp, Aengus Stewart, Havard Danielsen, Marco Novelli, Ian Tomlinson, Charles Swanton
Chromosomal instability (CIN) contributes to cancer evolution, intratumor heterogeneity, and drug resistance. CIN is driven by chromosome segregation errors and a tolerance phenotype that permits the propagation of aneuploid genomes. Through genomic analysis of colorectal cancers and cell lines, we find frequent loss of heterozygosity and mutations in BCL9L in aneuploid tumors. BCL9L deficiency promoted tolerance of chromosome missegregation events, propagation of aneuploidy, and genetic heterogeneity in xenograft models likely through modulation of Wnt signaling...
January 9, 2017: Cancer Cell
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