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https://www.readbyqxmd.com/read/30104415/germline-and-somatic-nf1-alterations-are-linked-to-increased-her2-expression-in-breast-cancer
#1
Xia Wang, Roope A Kallionpää, Patrick R Gonzales, Dhananjay A Chitale, Renee N Tousignant, Jacob P Crowley, Zhihua Chen, Sean J Yoder, Jaishri O Blakeley, Maria T Acosta, Bruce R Korf, Ludwine M Messiaen, Michael A Tainsky
NF1 germline mutation predisposes to breast cancer. NF1 mutations have also been proposed as oncogenic drivers in sporadic breast cancers. To understand the genomic and histological characteristics of these breast cancers, we analyzed the tumors with NF1 germline mutations and also examined the genomic and proteomic profiles of unselected tumors. Among 14 breast cancer specimens from 13 women affected with neurofibromatosis type 1 (NF1), 9 samples (NF+BrCa) underwent genomic copy number (CN) and targeted sequencing analysis...
August 13, 2018: Cancer Prevention Research
https://www.readbyqxmd.com/read/30098220/the-modification-of-mitochondrial-energy-metabolism-and-histone-of-goat-somatic-cells-under-small-molecules-compounds-induction
#2
Lanyu Li, Dandan Zhang, Yanyan Ren, Sheng Ye, Beibei Zheng, Shulin Liu, Jam Zaheer Ahmed, Mengmei Li, Deshun Shi, Ben Huang
In recent years, induced pluripotent stem cells (iPSCs) technique is able to allow us to generate pluripotency from somatic cells in vitro through the over expression of several transcription factors. Normally, viral vectors and transcription factors are commonly used on iPSC technique, which could cause many barriers on further application. In this study, we attempt to process a new method to obtain pluripotency from goat somatic cells in vitro under fully chemically defined condition. The results showed that chemically induced pluripotent stem cells-like cells (CiPSC-like cells) colonies were generated from goat ear fibroblasts by fully small-molecule compounds...
August 11, 2018: Reproduction in Domestic Animals, Zuchthygiene
https://www.readbyqxmd.com/read/30097516/the-homeobox-transcription-factor-msx2-partially-mediates-the-effects-of-bone-morphogenetic-protein-4-bmp4-on-somatic-cell-reprogramming
#3
Lilong Lin, Lining Liang, Xiao Yang, Hao Sun, Yuan Li, Duanqing Pei, Hui Zheng
Bone morphogenetic proteins (BMPs) induce the mesenchymal-epithelial transition (MET) and thereby enhance the generation of induced pluripotent stem cells (iPSCs). However, BMPs are also signaling molecules critical for arresting reprogramming at the pre-iPSC state. In the current study, using mouse embryonic fibroblasts, we found that the time- and concentration-dependent effects of BMPs on reprogramming are mediated by Msh homeobox 2 (MSX2), a homeobox-containing transcription factor. BMPs up-regulated Msx2 by activating SMAD1/5, and MSX2 then directly bound to the promoters and up-regulated the expression of the cadherin 1 ( Cdh1 also known as E-cadherin ), GATA-binding protein 3 ( Gata3 ), and Nanog genes...
August 10, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/30096312/divergent-routes-toward-wnt-and-r-spondin-niche-independency-during-human-gastric-carcinogenesis
#4
Kosaku Nanki, Kohta Toshimitsu, Ai Takano, Masayuki Fujii, Mariko Shimokawa, Yuki Ohta, Mami Matano, Takashi Seino, Shingo Nishikori, Keiko Ishikawa, Kenta Kawasaki, Kazuhiro Togasaki, Sirirat Takahashi, Yasutaka Sukawa, Hiroki Ishida, Shinya Sugimoto, Hirofumi Kawakubo, Jihoon Kim, Yuko Kitagawa, Shigeki Sekine, Bon-Kyoung Koo, Takanori Kanai, Toshiro Sato
Recent sequencing analyses have shed light on heterogeneous patterns of genomic aberrations in human gastric cancers (GCs). To explore how individual genetic events translate into cancer phenotypes, we established a biological library consisting of genetically engineered gastric organoids carrying various GC mutations and 37 patient-derived organoid lines, including rare genomically stable GCs. Phenotype analyses of GC organoids revealed divergent genetic and epigenetic routes to gain Wnt and R-spondin niche independency...
August 9, 2018: Cell
https://www.readbyqxmd.com/read/30091462/functional-characterization-of-recurrent-foxa2-mutations-seen-in-endometrial-cancers
#5
Robert Neff, Craig M Rush, Blair Smith, Floor J Backes, David E Cohn, Paul J Goodfellow
FOXA2, a member of the forkhead family of DNA-binding proteins, is frequently mutated in uterine cancers. Most of the mutations observed in uterine cancers are frameshifts and stops. FOXA2 is considered to be a driver gene in uterine cancers, functioning as a haploinsufficient tumor suppressor. The functional consequences of FOXA2 mutations, however, have not yet been determined. We evaluated the effects that frameshift mutations as well as a recurrent missense mutation have on FOXA2 transcriptional activity...
August 9, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/30090184/trichostatin-a-restores-expression-of-adherens-and-tight-junction-proteins-during-transforming-growth-factor-%C3%AE-mediated-epithelial-to-mesenchymal-transition
#6
Darshini A Ganatra, Abhay R Vasavada, Nair G Vidya, Devarshi U Gajjar, Sankaranarayanan Rajkumar
Purpose: Adherens junctions and polarity markers play an important role in maintaining epithelial phenotype but get altered during the epithelial-mesenchymal transition (EMT). Alterations of these markers during EMT of lens epithelial cell (LEC) can lead to vision compromising conditions. The aim of this study was to examine if Trichostatin-A (TSA), a histone deacetylase inhibitor, can prevent EMT by restoring the adherens junction complex in LEC. Methods: Fetal human lens epithelial cell line (FHL124) was used...
July 2018: Journal of Ophthalmic & Vision Research
https://www.readbyqxmd.com/read/30089731/frequent-basal-cell-cancer-development-is-a-clinical-marker-for-inherited-cancer-susceptibility
#7
Hyunje G Cho, Karen Y Kuo, Shufeng Li, Irene Bailey, Sumaira Aasi, Anne Lynn S Chang, Anthony E Oro, Jean Y Tang, Kavita Y Sarin
Innate DNA repair mechanisms play a critical role in protecting skin keratinocytes from UV mutagenesis and skin cancer development. We hypothesized that individuals who develop frequent skin cancers may harbor germline defects in DNA repair genes and have increased predisposition to internal malignancies. We enrolled 61 patients with unusually frequent basal cell carcinoma (BCC) development, seen at Stanford Hospital and Clinics from January 2005 until December 2015, for germline analysis of 29 DNA repair genes...
August 9, 2018: JCI Insight
https://www.readbyqxmd.com/read/30086764/targeted-next-generation-sequencing-identifies-clinically-relevant-somatic-mutations-in-a-large-cohort-of-inflammatory-breast-cancer
#8
Xu Liang, Sophie Vacher, Anais Boulai, Virginie Bernard, Sylvain Baulande, Mylene Bohec, Ivan Bièche, Florence Lerebours, Céline Callens
BACKGROUND: Inflammatory breast cancer (IBC) is the most aggressive form of primary breast cancer. Using a custom-made breast cancer gene sequencing panel, we investigated somatic mutations in IBC to better understand the genomic differences compared with non-IBC and to consider new targeted therapy in IBC patients. METHODS: Targeted next-generation sequencing (NGS) of 91 candidate breast cancer-associated genes was performed on 156 fresh-frozen breast tumor tissues from IBC patients...
August 7, 2018: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/30068014/-outcomes-after-prophylactic-total-gastrectomy-for-hereditary-diffuse-gastric-cancer
#9
Dimitrios Pantelis, Philipp Lingohr, Robert Hueneburg, Isabel Spier, Tim Vilz, Jan F Lau, Jacob Nattermann, Stefan Aretz, Christian P Strassburg, Jörg C Kalff
INTRODUCTION: Prophylactic total gastrectomy is the treatment of choice in patients with germline mutation in the CDH1 gene and therefore high risk for hereditary diffuse gastric cancer (HDGC). Minimally invasive techniques have been established in recent years for treatment of gastric cancer. METHODS: We report findings with 12 patients with proven CDH1 mutation who underwent multidisciplinary treatment between 2013 and 3/2018 in our centre for hereditary tumour diseases, followed by prophylactic total gastrectomy in our department...
August 1, 2018: Zentralblatt Für Chirurgie
https://www.readbyqxmd.com/read/30067950/epithelial-to-mesenchymal-transition-related-transcription-factors-are-upregulated-in-ependymomas-and-correlate-with-a-poor-prognosis
#10
Prit Benny Malgulwar, Aruna Nambirajan, Pankaj Pathak, Madhu Rajeshwari, Vaishali Suri, Chitra Sarkar, Manmohan Singh, Mehar Chand Sharma
Epithelial-to-mesenchymal transition (EMT) plays an important role in invasion and metastasis of various cancers including gliomas. EMT has also been linked to cancer stem cells and resistance to chemotherapy. An initial in-silico data mining in a published ependymoma (EPN) patient series (GSE21687) revealed upregulation of EMT-Transcription factors (EMT-TFs) in tumor samples. Further, quantitative real-time polymerase chain reaction (q-RT-PCR) based gene expression analysis of EMT-TFs in 96 EPNs showed significant up-regulation of SNAI1, SNAI2, ZEB1, and TWIST1 as compared to normal brain, associated with upregulation of CDH2/N-Cadherin and downregulation of CDH1/E-Cadherin...
July 29, 2018: Human Pathology
https://www.readbyqxmd.com/read/30066183/e-cadherin-deficient-cells-have-synthetic-lethal-vulnerabilities-in-plasma-membrane-organisation-dynamics-and-function
#11
Tanis D Godwin, S Thomas Kelly, Tom P Brew, Nicola M Bougen-Zhukov, Andrew B Single, Augustine Chen, Cassie E Stylianou, Lawrence D Harris, Sophie K Currie, Bryony J Telford, Henry G Beetham, Gary B Evans, Michael A Black, Parry J Guilford
BACKGROUND: The E-cadherin gene (CDH1) is frequently mutated in diffuse gastric cancer and lobular breast cancer, and germline mutations predispose to the cancer syndrome Hereditary Diffuse Gastric Cancer. We are taking a synthetic lethal approach to identify druggable vulnerabilities in CDH1-mutant cancers. METHODS: Density distributions of cell viability data from a genome-wide RNAi screen of isogenic MCF10A and MCF10A-CDH1-/- cells were used to identify protein classes affected by CDH1 mutation...
July 31, 2018: Gastric Cancer
https://www.readbyqxmd.com/read/30063010/mir-217-is-involved-in-the-carcinogenesis-of-gastric-cancer-by-down-regulating-cdh1-expression
#12
Wei Li, Yu-Qiang Gao
GC is one of the most leading malignancies all over the world, and is also the leading cause of cancer-related mortalities. At present, GC remains difficult to diagnose at an early stage. In this study, we first detected the expression of 9 selected miRNAs in the exosomes from 67 GC patients' circular exosomes and found 4 miRNAs level was significantly altered. Meanwhile, one out of 4 candidate miRNAs also had a higher expression in the GC tissue samples, and negative correlated with CDH1 expression. Predicted by bioinformatics tools, confirmed by dual luciferase assay and immunoblotting, we identified that CDH1 is a direct target of miR-217...
July 2018: Kaohsiung Journal of Medical Sciences
https://www.readbyqxmd.com/read/30056565/clinicopathological-and-prognostic-significance-of-ras-association-and-pleckstrin-homology-domains-1-raph1-in-breast-cancer
#13
Sasagu Kurozumi, Chitra Joseph, Sultan Sonbul, Mohammed A Aleskandarany, Marian Pigera, Mansour Alsaleem, Sami Alsaeed, Yousif Kariri, Christopher C Nolan, Maria Diez-Rodriguez, Simon Johnston, Nigel P Mongan, Takaaki Fujii, Ken Shirabe, Stewart G Martin, Ian O Ellis, Andrew R Green, Emad A Rakha
BACKGROUND: Ras association and pleckstrin homology domains 1 (RAPH1) is involved in cytoskeleton regulation and re-epithelialisation in invasive carcinoma and, therefore, may play a key role in carcinogenesis and metastasis. We, herein, investigated the biological and clinical significance of RAPH1 in breast cancer using large annotated cohorts. METHODS: The clinicopathological and prognostic significance of RAPH1 was assessed at the genomic and transcriptomic levels using The Cancer Genome Atlas (TCGA) dataset (n = 1039) and the results were validated using the Molecular taxonomy of breast cancer international consortium (METABRIC) cohort (n = 1980)...
July 28, 2018: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/30054569/dna-breakpoint-assay-reveals-a-majority-of-gross-duplications-occur-in-tandem-reducing-vus-classifications-in-breast-cancer-predisposition-genes
#14
Marcy E Richardson, Hansook Chong, Wenbo Mu, Blair R Conner, Vickie Hsuan, Sara Willett, Stephanie Lam, Pei Tsai, Tina Pesaran, Adam C Chamberlin, Min-Sun Park, Phillip Gray, Rachid Karam, Aaron Elliott
PURPOSE: Gross duplications are ambiguous in terms of clinical interpretation due to the limitations of the detection methods that cannot infer their context, namely, whether they occur in tandem or are duplicated and inserted elsewhere in the genome. We investigated the proportion of gross duplications occurring in tandem in breast cancer predisposition genes with the intent of informing their classifications. METHODS: The DNA breakpoint assay (DBA) is a custom, paired-end, next-generation sequencing (NGS) method designed to capture and detect deep-intronic DNA breakpoints in gross duplications in BRCA1, BRCA2, ATM, CDH1, PALB2, and CHEK2...
July 28, 2018: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/30050310/promoter-methylation-analysis-of-cdh1-and-p14arf-genes-in-patients-with-urothelial-bladder-cancer
#15
Bayram Bayramov, Sezgin Gunes, Recep Buyukalpelli, Oğuz Aydın, Ralf Henkel
Background/aim: Urothelial bladder cancer arises from the accumulation of multiple epigenetic and genetic changes. We aimed to investigate the specificity and sensitivity of gene-specific promoter methylation of CDH1 and p14ARF genes in the early diagnosis of bladder cancer and compare those with other diagnostic tests in our population. Patients and methods: In the current study, 65 patients with urothelial bladder cancer and 35 controls without any history of cancer were recruited...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/30047225/zeb1-and-zeb2-transcription-factors-are-potential-therapeutic-targets-of-canine-mammary-cancer-cells
#16
Pedro L P Xavier, Yonara G Cordeiro, Arina L Rochetti, Juliano R Sangalli, Debora A P C Zuccari, Juliano C Silveira, Fabiana F Bressan, Heidge Fukumasu
Mammary tumours are the most frequent in female dogs as in women and half are malignant. Tumorigenicity and invasiveness are important acquired characteristics for the development and progression of cancers and could be regulated by transcription factors associated with epithelial-mesenchymal transition (EMT) as ZEB1, ZEB2, SNAI1, SLUG and STAT3. Thus, here, we evaluate the expression of EMT-associated transcription factors in canine mammary cancer (CMC) cell lines characterized for invasiveness and tumorigenicity to determine if these could be considered good targets for future development of therapies...
July 25, 2018: Veterinary and Comparative Oncology
https://www.readbyqxmd.com/read/30041611/mutation-allele-frequency-threshold-does-not-affect-prognostic-analysis-using-next-generation-sequencing-in-oral-squamous-cell-carcinoma
#17
Jie Ma, Yong Fu, Yao-Yao Tu, Ying Liu, Yi-Ran Tan, Wu-Tong Ju, Curtis R Pickering, Jeffrey N Myers, Zhi-Yuan Zhang, Lai-Ping Zhong
BACKGROUND: With the development of sequencing technologies, there may be some disputes on sequencing analysis. The aim of this study was to investigate different allele frequency thresholds of mutations in targeted genes on prognostic analyses using a panel of cancer associated gene exons (CAGE) in oral squamous cell carcinoma (OSCC). METHODS: Forty-six patients were included in this study. Twelve genes were sequenced and analyzed using next-generation sequencing from formalin-fixed paraffin-embedded tissues...
July 24, 2018: BMC Cancer
https://www.readbyqxmd.com/read/30035249/survival-outcomes-by-tp53-mutation-status-in-metastatic-breast-cancer
#18
Funda Meric-Bernstam, Xiaofeng Zheng, Maryam Shariati, Senthil Damodaran, Chetna Wathoo, Lauren Brusco, Mehmet Esat Demirhan, Coya Tapia, Agda Karina Eterovic, Reva K Basho, Naoto T Ueno, Filip Janku, Aysegul Sahin, Jordi Rodon, Russell Broaddus, Tae-Beom Kim, John Mendelsohn, Kenna R Mills Shaw, Debu Tripathy, Gordon B Mills, Ken Chen
Purpose: We sought to determine the significant genomic alterations in patients with metastatic breast cancer (MBC), and survival outcomes in common genotypes. Patients and Methods: High-depth next generation sequencing was performed for 202 genes in tumor and normal DNA from 257 patients with MBC, including 165 patients with ER/PR+ HER2- (hormone receptor positive, HR+ positive), 32 patients with HER2+ and 60 patients with triple negative (ER/PR/HER2-) cancer. Kaplan Meier survival analysis was performed in our discovery set, in breast cancer patients analyzed in The Cancer Genome Atlas, and in a separate cohort of 98 patients with MBC who underwent clinical genomic testing...
2018: JCO Precision Oncology
https://www.readbyqxmd.com/read/30034626/circulating-tumor-cells-mirror-bone-metastatic-phenotype-in-prostate-cancer
#19
Andreas Josefsson, Karin Larsson, Marianne Månsson, Jens Björkman, Eva Rohlova, Daniel Åhs, Helena Brisby, Jan-Erik Damber, Karin Welén
Circulating tumor cells (CTCs) are promising biomarkers in prostate cancer (PC) because they derive from primary tumor and metastatic tissues. In this study, we used quantitative real-time PCR (qPCR) to compare the expression profiles of 41 PC-related genes between paired CTC and spinal column metastasis samples from 22 PC patients that underwent surgery for spinal cord compression. We observed good concordance between the gene expression profiles in the CTC and metastasis samples in most of the PC patients...
June 29, 2018: Oncotarget
https://www.readbyqxmd.com/read/30023340/analysis-of-hierarchical-organization-in-gene-expression-networks-reveals-underlying-principles-of-collective-tumor-cell-dissemination-and-metastatic-aggressiveness-of-inflammatory-breast-cancer
#20
Shubham Tripathi, Mohit Kumar Jolly, Wendy A Woodward, Herbert Levine, Michael W Deem
Clusters of circulating tumor cells (CTCs), despite being rare, may account for more than 90% of metastases. Cells in these clusters do not undergo a complete epithelial-to-mesenchymal transition (EMT), but retain some epithelial traits as compared to individually disseminating tumor cells. Determinants of single cell dissemination versus collective dissemination remain elusive. Inflammatory breast cancer (IBC), a highly aggressive breast cancer subtype that chiefly metastasizes via CTC clusters, is a promising model for studying mechanisms of collective tumor cell dissemination...
2018: Frontiers in Oncology
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