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p53 cancer mutation

Parvin A Barbhuiya, Arif Uddin, Supriyo Chakraborty
The TP73 gene is considered as one of the members of TP53 gene family and shows much homology to p53 gene. TP73 gene plays a pivotal role in cancer studies in addition to other biological functions. Codon usage bias (CUB) is the phenomenon of unequal usage of synonymous codons for an amino acid wherein some codons are more frequently used than others and it reveals the evolutionary relationship of a gene. Here, we report the pattern of codon usage in TP73 gene using various bioinformatic tools as no work was reported yet...
October 11, 2018: Gene
Kun Tian, Emyr Bakker, Michelle Hussain, Alice Guazzelli, Hasen Alhebshi, Parisa Meysami, Constantinos Demonacos, Jean-Marc Schwartz, Luciano Mutti, Marija Krstic-Demonacos
BACKGROUND: Malignant pleural mesothelioma (MPM) is an orphan disease that is difficult to treat using traditional chemotherapy, an approach which has been effective in other types of cancer. Most chemotherapeutics cause DNA damage leading to cell death. Recent discoveries have highlighted a potential role for the p53 tumor suppressor in this disease. Given the pivotal role of p53 in the DNA damage response, here we investigated the predictive power of the p53 interactome model for MPM patients' stratification...
October 13, 2018: Journal of Translational Medicine
Ignacio A Rodriguez-Brenes, Natalia L Komarova, Dominik Wodarz
Genome instability is a characteristic of most cancers, contributing to the acquisition of genetic alterations that drive tumor progression. One important source of genome instability is linked to telomere dysfunction in cells with critically short telomeres that lack p53-mediated surveillance of genomic integrity. Here we research the probability that cancer emerges through an evolutionary pathway that includes a telomere-induced phase of genome instability. To implement our models we use a hybrid stochastic-deterministic approach, which allows us to perform large numbers of simulations using biologically realistic population sizes and mutation rates, circumventing the traditional limitations of fully stochastic algorithms...
October 10, 2018: Journal of Theoretical Biology
Luting Yang, Shaolong Zhang, Gang Wang
Keratin 17 (K17) is a type I intermediate filament mainly expressed in the basal cells of epithelia. As a multifaceted cytoskeletal protein, K17 regulates a myriad of biological processes, including cell proliferation and growth, skin inflammation and hair follicle cycling. Aberrant overexpression of K17 is found in various diseases ranging from psoriasis to malignancies such as breast, cervical, oral squamous and gastric carcinomas. Moreover, genetic mutation in KRT17 is related to tissue-specific diseases, represented by steatocystoma multiplex and pachyonychia congenita...
October 10, 2018: Journal of Pathology
Atif Ali Hashmi, Samreen Naz, Shumaila Kanwal Hashmi, Zubaida Fida Hussain, Muhammad Irfan, Erum Yousuf Khan, Naveen Faridi, Amir Khan, Muhammad Muzzammil Edhi
Background: p16 and p53 genes are frequently mutated in triple negative breast cancer & prognostic value of these mutations have been shown; however, their role as immunohistochemical overexpression has not been fully validated. Therefore we aimed to evaluate the association of p16 and p53 overexpression in triple negative breast cancer with various prognostic parameters. Methods: Total 150 cases of triple negative breast cancers were selected from records of pathology department archives that underwent surgeries at Liaquat National hospital, Karachi from January 2008 till December 2013...
2018: BMC Clinical Pathology
Christine J Ko, Peggy Myung, David J Leffell, Jean-Christophe Bourdon
p53 is considered the guardian of the genome and as such has numerous functions. The TP53 gene is the most commonly mutated gene in cancer, and yet the exact biological significance of such mutations remains unclear. There are at least 12 different isoforms of p53, and the complexity of the p53 pathway may be in part related to these isoforms. Prior research has often not teased out what isoforms of p53 are being studied, and there is evidence in the literature that p53 isoforms are expressed differently. In this paper, we document the staining pattern of p53β isoforms in the skin and correlate it with mutational status in a subgroup of squamous proliferations of the skin...
October 10, 2018: Journal of Clinical Pathology
Roseane Guimarães Ferreira, Magda Vieira Cardoso, Karine Maria de Souza Furtado, Kaio Murilo Monteiro Espíndola, Ruanderson Pereira Amorim, Marta Chagas Monteiro
Aflatoxin B1 (AFB1) is currently the most commonly studied mycotoxin due to its great toxicity, its distribution in a wide variety of foods such as grains and cereals and its involvement in the development of + (hepatocellular carcinoma; HCC). HCC is one of the main types of liver cancer, and has become a serious public health problem, due to its high incidence mainly in Southeast Asia and Africa. Studies show that AFB1 acts in synergy with other risk factors such as hepatitis B and C virus leading to the development of HCC through genetic and epigenetic modifications...
September 15, 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
Giovanna Butera, Raffaella Pacchiana, Nidula Mullappilly, Marilena Margiotta, Stefano Bruno, Paola Conti, Chiara Riganti, Massimo Donadelli
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and devastating human malignancies. In about 70% of PDACs the tumor suppressor gene TP53 is mutated generally resulting in conformational changes of mutant p53 (mutp53) proteins, which acquire oncogenic functions triggering aggressiveness of cancers and alteration of energetic metabolism. Here, we demonstrate that mutant p53 prevents the nuclear translocation of the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) stabilizing its cytoplasmic localization, thus supporting glycolysis of cancer cells and inhibiting cell death mechanisms mediated by nuclear GAPDH...
October 5, 2018: Biochimica et biophysica acta. Molecular cell research
Yu Gao, Huijuan Zhang, Yingying Zhang, Tingting Lv, Lu Zhang, Ziying Li, Xiaodong Xie, Fengqiao Li, Haijun Chen, Lee Jia
The outcome of molecular targeted therapies is restricted by the ambiguous molecular subtypes of non-small cell lung cancer (NSCLC) which are difficult to be defined with druggable mutations, and the inevitable emergence of drug-resistance. Here we used the Cu-catalyzed click chemistry to synthesize a chitosan-based self-assembled nanotheranostics (CE7Ns) composing of a near-infrared (NIR) fluorescent photosensitizer Cy7 and molecular targeted drug erlotinib. The well-characterized CE7Ns can release erlotinib and Cy7 fast under acidic condition in the presence of lysozyme, distinguish three molecular subtypes of NSCLC and specifically bind to the erlotinib-sensitive EGFR-mutated PC-9 cells...
October 8, 2018: Molecular Pharmaceutics
Constantinos G Broustas, Kevin M Hopkins, Sunil K Panigrahi, Li Wang, Renu K Virk, Howard B Lieberman
RAD9A plays an important role in prostate tumorigenesis and metastasis related phenotypes. The protein classically functions as part of the RAD9A-HUS1-RAD1 complex but can also act independently. RAD9A can selectively transactivate multiple genes, including CDKN1A and NEIL1 by binding p53-consensus sequences in or near promoters. RAD9A is overexpressed in human prostate cancer specimens and cell lines; its expression correlates with tumor progression. Silencing RAD9A in prostate cancer cells impairs their ability to form tumors in vivo and migrate as well as grow anchorage-independently in vitro...
October 6, 2018: Carcinogenesis
Sigrid Regauer, Karl Kashofer, Olaf Reich
The impact of TP53 gene mutations in recurrent HPV-negative vulvar squamous cell carcinomas is unclear. TP53 gene mutations were analyzed in archival tissues of 24 primary squamous cell carcinoma and local vulvar recurrences arising in chronic inflammatory dermatoses by analyzing the full coding sequence of the TP53 gene and correlated with disease-free survival. After resection of the primary squamous cell carcinoma with clear margins 19/24 patients had one and 5/24 had multiple recurrences. The first recurrence occurred after median of 46 months (range 12-180 months)...
October 5, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
Siqin Gaowa, Manabu Futamura, Masayuki Tsuneki, Hiroki Kamino, Jesse Y Tajima, Ryutaro Mori, Hirofumi Arakawa, Kazuhiro Yoshida
Mitochondria-eating protein (Mieap), encoded by a p53-target gene, plays an important role in mitochondrial quality control (MQC). Mieap has been reported to have a critical role in tumor suppression in colorectal cancer. Here, we investigated its role as a tumor suppressor in breast cancer. The enforced-expression of exogenous Mieap in breast cancer cells induced caspase-dependent apoptosis, with activation of both caspase-3/7 and caspase-9. Immunohistochemistry revealed endogenous Mieap in the cytoplasm in 24/75 (32%) invasive ductal carcinomas (IDCs), 15/27 (55...
October 5, 2018: Cancer Science
Nathan A Ungerleider, Sonia G Rao, Ashkan Shahbandi, Douglas Yee, Tianhua Niu, Wesley D Frey, James G Jackson
BACKGROUND: Previous studies on the role of TP53 mutation in breast cancer treatment response and survival are contradictory and inconclusive, limited by the use of different endpoints to determine clinical significance and by small sample sizes that prohibit stratification by treatment. METHODS: We utilized large datasets to examine overall survival according to TP53 mutation status in patients across multiple clinical features and treatments. RESULTS: Confirming other studies, we found that in all patients and in hormone therapy-treated patients, TP53 wild-type status conferred superior 5-year overall survival, but survival curves crossed at 10 or more years...
October 1, 2018: Breast Cancer Research: BCR
Yudong Wang, Zhijie Wang, Sarina Piha-Paul, Filip Janku, Vivek Subbiah, Naiyi Shi, Kenneth Hess, Russell Broaddus, Baoen Shan, Aung Naing, David Hong, Apostolia M Tsimberidou, Daniel Karp, Charles Lu, Vali Papadimitrakopoulou, John Heymach, Funda Meric-Bernstam, Siqing Fu
KRAS and TP53 mutations, which are the most common genetic drivers of tumorigenesis, are still considered undruggable targets. Therefore, we analyzed these genetic aberrations in metastatic non-small cell lung cancer (NSCLC) for the development of potential therapeutics. One hundred eighty-five consecutive patients with metastatic NSCLC in a phase 1 trial center were included. Their genomic aberrations, clinical characteristics, survivals, and phase 1 trial therapies were analyzed. About 10%, 18%, 36%, and 36% of the patients had metastatic KRAS +/ TP53 +, KRAS +/ TP53 -, KRAS -/ TP53 +, and KRAS -/ TP53 - NSCLC, respectively...
September 7, 2018: Oncotarget
Yi Fang, Xiao Ma, Jing Zeng, Yanwen Jin, Yong Hu, Jinjing Wang, Ran Liu, Cheng Cao
BACKGROUND/AIMS: The purpose of the study was to investigate the altered driver genes and signal pathways during progression of papillary thyroid cancer (PTC) via next-generation sequencing technology. METHODS: The DNA samples for whole exome sequencing (WES) analyses were extracted from 11 PTC tissues and adjacent normal tissues samples. Direct Sanger sequencing was applied to validate the identified mutations. RESULTS: Among the 11 pairs of tissues specimens, 299 single nucleotide variants (SNVs) in 75 genes were identified...
October 2, 2018: Cellular Physiology and Biochemistry
Elisabeth Maritschnegg, Nicole Heinzl, Stuart Wilson, Simon Deycmar, Markus Niebuhr, Lukas Klameth, Barbara M Holzer, Katarzyna Koziel, Nicole Concin, Robert Zeillinger
A growing number of diseases is being linked to protein misfolding and amyloid formation. Recently, also p53 was shown to associate into amyloid aggregates, raising the question whether cancer development is associated with protein aggregation as well. However, a lack in suitable tools was hampering the evaluation of their clinical relevance. Herein we report an enzyme-linked immunosorbent assay (ELISA) system, based on a poly-ionic high molecular weight ligand, which specifically captures aggregated oligomers and amyloid proteins...
October 2, 2018: Analytical Chemistry
Omar Youssef, Aija Knuuttila, Päivi Piirilä, Tom Böhling, Virinder Sarhadi, Sakari Knuutila
BACKGROUND: Genetic alterations occurring in lung cancer are the basis for defining molecular subtypes and essential for targeted therapies. Exhaled breath condensate (EBC) is a form of non-invasive sample that, amongst components, contains DNA from pulmonary tissue. Next-generation sequencing (NGS) was herein used to analyze mutations in EBC from patients with lung cancer. MATERIALS AND METHODS: EBC was collected from 26 patients with cancer and 20 healthy controls...
October 2018: Anticancer Research
Ileana Hernández-Reséndiz, Juan Carlos Gallardo-Pérez, Ambar López-Macay, Diana Xochiquetzal Robledo-Cadena, Enrique García-Villa, Patricio Gariglio, Emma Saavedra, Rafael Moreno-Sánchez, Sara Rodríguez-Enríquez
Mutations in p53 are strongly associated with several highly malignant cancer phenotypes but its role in regulating energy metabolism has not been completely elucidated. The effect on glycolysis and oxidative phosphorylation (OxPhos) of mutant p53R248Q overexpression in HeLa cells (HeLa-M) was analyzed and compared with cells overexpressing wild-type p53 (HeLa-H) and nontransfected cells containing negligible p53 levels (HeLa-L). p53 R248Q overexpression induced early cell detachment during in vitro growth; however, detached HeLa-M cells showed high viability, shorter generation time and significant diminution in the adhesion proteins E-cadherin and β-catenin versus HeLa-H and HeLa-L cells...
September 10, 2018: Journal of Cellular Physiology
Marc Payton, Hung-Kam Cheung, Maria Stefania S Ninniri, Christian Marinaccio, William C Wayne, Kelly Hanestad, John D Crispino, Gloria Juan, Angela Coxon
Aurora kinase A and B have essential and non-overlapping roles in mitosis, with elevated expression in a subset of human cancers, including acute myeloid leukemia (AML). In this study, pan-aurora kinase inhibitor (AKI) AMG 900 distinguishes itself as an anti-leukemic agent that is more uniformly potent against a panel of AML cell lines than are isoform-selective AKIs and classic AML drugs. AMG 900 inhibited AML cell growth by inducing polyploidization and/or apoptosis. AMG 900 and aurora-B selective inhibitor AZD1152-hQPA showed comparable cellular effects on AML lines that do not harbor a FLT3-ITD mutation...
September 28, 2018: Molecular Cancer Therapeutics
Ya Hua Chim, Louise M Mason, Nicola Rath, Michael F Olson, Manlio Tassieri, Huabing Yin
The increasingly recognised importance of viscoelastic properties of cells in pathological conditions requires rapid development of advanced cell microrheology technologies. Here, we present a novel Atomic Force Microscopy (AFM)-microrheology (AFM2 ) method for measuring the viscoelastic properties in living cells, over a wide range of continuous frequencies (0.005 Hz ~ 200 Hz), from a simple stress-relaxation nanoindentation. Experimental data were directly analysed without the need for pre-conceived viscoelastic models...
September 27, 2018: Scientific Reports
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