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https://www.readbyqxmd.com/read/29050359/next-generation-sequencing-in-chronic-lymphocytic-leukemia-recent-findings-and-new-horizons
#1
REVIEW
Ana E Rodríguez-Vicente, Vasilis Bikos, María Hernández-Sánchez, Jitka Malcikova, Jesús-María Hernández-Rivas, Sarka Pospisilova
The rapid progress in next-generation sequencing technologies has significantly contributed to our knowledge of the genetic events associated with the development, progression and treatment resistance of chronic lymphocytic leukemia patients. Together with the discovery of new driver mutations, next-generation sequencing has revealed an immense degree of both intra- and inter-tumor heterogeneity and enabled us to describe marked clonal evolution. Advances in immunogenetics may be implemented to detect minimal residual disease more sensitively and to track clonal B cell populations, their dynamics and molecular characteristics...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29050326/different-effection-of-p-1125val-ala-and-rs11954856-in-apc-on-wnt-signaling-pathway
#2
Fei-Feng Li, Zhi-Xun Zhao, Peng Yan, Song Wang, Zheng Liu, Qiong Zhang, Xiao-Ning Zhang, Chang-Hao Sun, Xi-Shan Wang, Gui-Yu Wang, Shu-Lin Liu
Colorectal cancer (CRC) is among the most common and fatal forms of solid tumors worldwide and more than two thirds of CRC and adenomas patients have APC gene mutations. APC is a key regulator in the Wnt/β-catenin signaling pathway but its roles in CRC remains to be elucidated. In this study, we compared APC genes between CRC patients and controls to determine possible associations of nucleotide changes in the APC gene with the pathways involved in CRC pathogenesis. All participants received physical and enteroscopic examinations...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29050263/the-prognostic-value-of-osteopontin-in-limited-stage-small-cell-lung-cancer-patients-and-its-mechanism
#3
Fanglei Liu, Chunxue Bai, Zhongliang Guo
Osteopontin (OPN) is known to be overexpressed in numerous carcinomas. Although abundant OPN has been reported to be correlated with poor survival in non-small cell lung cancer (NSCLC) but their clinical and prognostic significance in SCLC remains unknown. In this study, RNA-sequencing was used to obtain gene expression data in SCLC tissue samples and OPN expression levels were then investigated using qPCR, immunohistochemical and Western blot. We found OPN was one of the most upregulated genes. Besides, the correlation of OPN with tumor clinicopathological characteristics was evaluated and we found OPN was associated with advanced tumor stages...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29050228/mutation-landscape-and-intra-tumor-heterogeneity-of-two-manecs-of-the-esophagus-revealed-by-multi-region-sequencing
#4
Wenqing Yuan, Zhen Liu, Wanjun Lei, Li Sun, Haijun Yang, Yu Wang, Shweta Ramdas, Xiao Dong, Ruiping Xu, Hong Cai, Jun Z Li, Yang Ke
Mixed adenoneuroendocrine carcinoma (MANEC) in the esophagus is an infrequent but highly malignant cancer with few known genomic alterations. We conducted whole-exome sequencing and whole-genome SNP genotyping for 4-6 tumor subregions and 5-6 adjacent normal tissue sites and 1-3 lymph node metastases in two esophageal MANECs to detect somatic mutations and copy number alterations, and to explore their spatial heterogeneity and underlying clonal structure. TP53 mutation, RB1 deletion or LOH, and PIK3CA, PTEN, KRAS, SOX2, DVL3, TP63 amplification appeared in all regions in both tumors...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29049475/potential-of-aqueous-humor-as-a-surrogate-tumor-biopsy-for-retinoblastoma
#5
Jesse L Berry, Liya Xu, A Linn Murphree, Subramanian Krishnan, Kevin Stachelek, Emily Zolfaghari, Kathleen McGovern, Thomas C Lee, Anders Carlsson, Peter Kuhn, Jonathan W Kim, David Cobrinik, James Hicks
Importance: Retinoblastoma (Rb) is one of the first tumors to have a known genetic etiology. However, because biopsy of this tumor is contraindicated, it has not been possible to define the effects of secondary genetic changes on the disease course. Objective: To investigate whether the aqueous humor (AH) of Rb eyes has sufficient tumor-derived DNA to perform genetic analysis of the tumor, including DNA copy number alterations. Design, Setting, and Participants: This investigation was a case series study at a tertiary care hospital (Children's Hospital Los Angeles) with a large Rb treatment center...
October 12, 2017: JAMA Ophthalmology
https://www.readbyqxmd.com/read/29049316/genomic-comparison-of-early-passage-conditionally-reprogrammed-breast-cancer-cells-to-their-corresponding-primary-tumors
#6
Akanksha S Mahajan, Bruna M Sugita, Anju N Duttargi, Francisco Saenz, Ewa Krawczyk, Justine N McCutcheon, Aline S Fonseca, Bhaskar Kallakury, Paula Pohlmann, Yuriy Gusev, Luciane R Cavalli
Conditionally reprogrammed cells (CRCs) are epithelial cells that are directly isolated from patients' specimens and propagated in vitro with feeder cells and a Rho kinase inhibitor. A number of these cells have been generated from biopsies of breast cancer patients, including ductal carcinoma in situ and invasive carcinomas. The characterization of their genomic signatures is essential to determine their ability to reflect the natural biology of their tumors of origin. In this study, we performed the genomic characterization of six newly established invasive breast cancer CRC cultures in comparison to the original patients' primary breast tumors (PBT) from which they derived...
2017: PloS One
https://www.readbyqxmd.com/read/29049091/tumor-microenvironment-and-models-of-ovarian-cancer-the-11th-biennial-rivkin-center-ovarian-cancer-research-symposium
#7
Karen McLean, Geeta Mehta
OBJECTIVE: The aim of this study was to review the latest research advances on the topics of the ovarian cancer tumor microenvironment and models of ovarian cancer. METHODS: In September 2016, a symposium of the leaders in the field of ovarian cancer research was convened to present and discuss current advances and future directions in ovarian cancer research. RESULTS: One session was dedicated to Tumor Microenvironment and Models of Ovarian Cancer, and included a keynote presentation from Anil Sood, MD, and an invited oral presentation from David Huntsman, MD...
October 18, 2017: International Journal of Gynecological Cancer
https://www.readbyqxmd.com/read/29048978/antitumor-effect-of-oral-cancer-vaccine-with-bifidobacterium-delivering-wt1-protein-to-gut-immune-system-is-superior-to-wt1-peptide-vaccine
#8
Toshiro Shirakawa, Koichi Kitagawa
Despite the revolutionary progress of immune checkpoint inhibitors (CPIs) for cancer immunotherapy, CPIs are effective only in a subset of patients. Combining CPIs and cancer vaccines to achieve better clinical outcomes is a reasonable approach since CPI enhances cancer vaccine-induced tumor-associated antigen (TAA) specific CTL. Among the various TAAs so far identified, WT1 protein is one of the most promising TAAs as a cancer vaccine target. Until now clinical trials of WT1 vaccine have demonstrated only modest clinical efficacy...
October 19, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/29048660/canonical-and-non-canonical-wnt-signaling-in-cancer-stem-cells-and-their-niches-cellular-heterogeneity-omics-reprogramming-targeted-therapy-and-tumor-plasticity-review
#9
Masaru Katoh
Cancer stem cells (CSCs), which have the potential for self-renewal, differentiation and de-differentiation, undergo epigenetic, epithelial-mesenchymal, immunological and metabolic reprogramming to adapt to the tumor microenvironment and survive host defense or therapeutic insults. Intra-tumor heterogeneity and cancer-cell plasticity give rise to therapeutic resistance and recurrence through clonal replacement and reactivation of dormant CSCs, respectively. WNT signaling cascades cross-talk with the FGF, Notch, Hedgehog and TGFβ/BMP signaling cascades and regulate expression of functional CSC markers, such as CD44, CD133 (PROM1), EPCAM and LGR5 (GPR49)...
September 19, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29048648/long-non-coding-rna-xist-regulates-pdcd4-expression-by-interacting-with-mir-21-5p-and-inhibits-osteosarcoma-cell-growth-and-metastasis
#10
Rui Zhang, Tian Xia
lncRNA-X-inactive specific transcript (lncRNA XIST) has been demonstrated to be a tumor suppressor involved in the pathogenesis and development of various cancers. However, the function of XIST and its working mechanism in osteosarcoma (OS) remain enigmatic. Firstly, we determined the expression of XIST in OS tissues and cell lines by quantitative reverse transcription-PCR (qRT-PCR) and explored whether aberrant XIST expression was associated with recurrence and short overall survival. Furthermore, the effects of XIST on osteosarcoma cells were studied by lentivirus mediated overexpression approach in vitro and in vivo...
September 19, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29047110/cytoskeleton-and-ecm-tumor-mutant-peptides-increased-protease-sensitivities-and-potential-consequences-for-the-hla-class-i-mutant-epitope-reservoir
#11
Blake M Callahan, Jay S Patel, Timothy J Fawcett, George Blanck
Cytoskeleton and extracellular matrix-related proteins (CECMPs) represent the most common class of cancer mutants, owing to the large size of their coding regions and the randomness of mutagenesis. We used a bioinformatics approach to assess the impact of amino acid (AA) substitutions on the sensitivity of CECMPs to proteases relevant to melanoma; and on the binding affinities for HLA class I. CECMP peptides with AA substitutions overwhelmingly reflect increased sensitivity to proteases implicated in melanoma development (MME, CTSS, MMP2, CTSD, CTSL) in comparison to the wild type peptide sequences...
October 19, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29046389/the-antibody-repertoire-of-colorectal-cancer
#12
Seong Won Cha, Stefano Bonissone, Seungjin Na, Pavel A Pevzner, Vineet Bafna
Immunotherapy is becoming increasingly important in the fight against cancers, utilizing and manipulating the body's immune response to treat tumors. Understanding the immune repertoire - the collection of immunological proteins - of treated and untreated cells is possible at the genomic, but technically difficult at the protein level. Standard protein databases do not include the highly divergent sequences of somatic rearranged immunoglobulin genes, and may lead to missed identifications in a mass spectrometry search...
October 18, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29046366/long-non-coding-rna-pvt1-indicates-a-poor-prognosis-of-glioma-and-promotes-cell-proliferation-and-invasion-via-target-ezh2
#13
Anqiang Yang, Handong Wang, Xiaobing Yang
Human glioma, as one of the malignant tumors of the central nervous system, its prognosis is poor, which is due to its genetic heterogeneity and our poor understanding of its underlying molecular mechanisms. This study aimed to assess the relationship between plasmacytoma variant translocation 1 (PVT1) and enhancer of zeste homolog 2 (EZH2), and their effects on the proliferation and invasion of glioma cells. The expression levels of PVT1 and EZH2 in human glioma tissues and cell lines were measured using qRT-PCR...
October 18, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/29046358/translationally-controlled-tumor-protein-is-required-for-the-fast-growth-of-toxoplasma-gondii-and-maintenance-of-its-intracellular-development
#14
Jun Zheng, Yaping Chen, Zhaoran Li, Shinuo Cao, Zhaoxia Zhang, Honglin Jia
Translationally controlled tumor protein (TCTP) is a highly conserved, multifunctional protein that has been implicated in a range of cell physiologic processes, especially cell growth and development. A TCTP-like gene has been identified in the Toxoplasma genome [Toxoplasma gondii TCTP (TgTCTP)], although its function remains unknown. The sequence analysis of TgTCTP indicated that it is a highly conserved protein in eukaryotes. We found that the expression level of TgTCTP in the virulent RH strain was significantly higher than that in the avirulent PLK strain...
October 18, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29046141/generation-and-characterization-of-a-bispecific-antibody-targeting-both-pd-1-and-c-met
#15
Yi Wu, Min Yu, Zujun Sun, Weihua Hou, Yuxiong Wang, Qingyun Yuan, Wei Mo
Bispecific antibodies, BsAbs, are molecules with the ability to bind to two different epitopes on the same or different antigens. The goal of this study was to create a novel bispecific antibody targeting both cellular-mesenchymal to epithelial transition factor(c-MET) and programmed death-1(PD-1) as an anti-cancer therapeutic candidate. Upon binding to the c-MET antigen on a tumor cell and the PD-1 antigen on a T cell, a BsAb can redirect T cells for tumor killing. Based on the original sequences of PD-1 and c-MET mAbs, a BsAb gene was designed, and cloned into the pCEP4 vector...
October 17, 2017: Protein and Peptide Letters
https://www.readbyqxmd.com/read/29045527/braf-mutant-colorectal-cancer-prognosis-treatment-and-new-perspectives
#16
E Sanz-Garcia, G Argiles, E Elez, J Tabernero
The MAPK cascade plays a crucial role in tumor cell proliferation and survival. Accumulating evidence suggests that mutations in the BRAF oncogene are not only associated with poor prognosis but also linked with less benefit when treated with anti-epidermal growth factor receptor (EGFR) antibodies in metastatic colorectal cancer (mCRC). Targeting this molecular aberration has thus become a matter of particular interest in mCRC drug development. In contrast to other malignances such as BRAF mutant (mt) melanoma, efficacy observed with BRAF inhibitors in mono-therapy in mCRC is poor...
July 24, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29045506/clinical-and-molecular-characterization-of-patients-with-cancers-of-unknown-primary-in-the-modern-era
#17
A M Varghese, A Arora, M Capanu, N Camacho, H H Won, A Zehir, J Gao, D Chakravarty, N Schultz, D S Klimstra, M Ladanyi, D M Hyman, D B Solit, M F Berger, L B Saltz
Background: On the basis of historical data, patients with cancers of unknown primary (CUP) are generally assumed to have a dismal prognosis with overall survival of less than one year. Treatment is typically cytotoxic chemotherapy guided by histologic features and the pattern of metastatic spread. The purpose of this study was to provide a clinical and pathologic description of patients with CUP in the modern era, to define the frequency of clinically actionable molecular alterations in this population, to determine how molecular testing can alter therapeutic decisions, and to investigate novel uses of next generation sequencing in the evaluation and treatment of patients with CUP...
September 26, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29045505/surfaceome-profiling-enables-isolation-of-cancer-specific-exosomal-cargo-in-liquid-biopsies-from-pancreatic-cancer-patients
#18
J Castillo, V Bernard, F A San Lucas, K Allenson, M Capello, D U Kim, P Gascoyne, F C Mulu, B M Stephens, J Huang, H Wang, A A Momin, R O Jacamo, M Katz, R Wolff, M Javle, G Varadhachary, I I Wistuba, S Hanash, A Maitra, H Alvarez
Background: Detection of circulating tumor DNA (ctDNA) can be limited due to their relative scarcity in circulation, particularly while patients are actively undergoing therapy. Exosomes provide a vehicle through which cancer-specific material can be enriched from the compendium of circulating non-neoplastic tissue-derived nucleic acids. We performed a comprehensive profiling of the pancreatic ductal adenocarcinoma (PDAC) exosomal "surfaceome" in order to identify surface proteins that will render liquid biopsies amenable to cancer-derived exosome enrichment for downstream molecular profiling...
September 25, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29045504/molecular-tumor-boards-current-practice-and-future-needs
#19
D L van der Velden, C M L van Herpen, H W M van Laarhoven, E F Smit, H J M Groen, S M Willems, P M Nederlof, M H G Langenberg, E Cuppen, S Sleijfer, N Steeghs, E E Voest
Background: due to rapid technical advances, steeply declining sequencing costs, and the ever-increasing number of targeted therapies, it can be expected that extensive tumor sequencing such as Whole Exome- and -Genome Sequencing will soon be applied in standard care. Clinicians will thus be confronted with increasingly complex genetic information and multiple test-platforms to choose from. General medical training, meanwhile, can hardly keep up with the pace of innovation. Consequently, there is a rapidly growing gap between clinical knowledge and genetic potential in cancer care...
September 27, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29044880/targeted-deep-sequencing-of-effusion-cytology-samples-is-feasible-informs-spatiotemporal-tumor-evolution-and-has-clinical-and-diagnostic-utility
#20
Jonas Leichsenring, Anna-Lena Volckmar, Martina Kirchner, Daniel Kazdal, Mark Kriegsmann, Fabian Stögbauer, Teresa Bockmayr, Frederick Klauschen, Felix J F Herth, Roland Penzel, Arne Warth, Peter Schirmacher, Volker Endris, Albrecht Stenzinger
During the course of disease, many cancer patients eventually present with metastatic disease including peritoneal or pleural spread. In this context, cytology specimens derived from ascites or pleural effusion may help to differentiate malignant from benign conditions and sometimes yield diagnosis of a malignancy. However, even when supported by immunohistochemistry, cytological interpretation can be challenging, especially if tumor cellularity is low. Here, we investigated whether targeted deep sequencing of formalin-fixed and paraffin embedded (FFPE) cytology specimens of cancer patients is feasible, and has diagnostic and clinical impact...
October 16, 2017: Genes, Chromosomes & Cancer
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