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https://www.readbyqxmd.com/read/28346444/genetic-variants-associated-with-mosaic-y-chromosome-loss-highlight-cell-cycle-genes-and-overlap-with-cancer-susceptibility
#1
Daniel J Wright, Felix R Day, Nicola D Kerrison, Florian Zink, Alexia Cardona, Patrick Sulem, Deborah J Thompson, Svanhvit Sigurjonsdottir, Daniel F Gudbjartsson, Agnar Helgason, J Ross Chapman, Steve P Jackson, Claudia Langenberg, Nicholas J Wareham, Robert A Scott, Unnur Thorsteindottir, Ken K Ong, Kari Stefansson, John R B Perry
The Y chromosome is frequently lost in hematopoietic cells, which represents the most common somatic alteration in men. However, the mechanisms that regulate mosaic loss of chromosome Y (mLOY), and its clinical relevance, are unknown. We used genotype-array-intensity data and sequence reads from 85,542 men to identify 19 genomic regions (P < 5 × 10(-8)) that are associated with mLOY. Cumulatively, these loci also predicted X chromosome loss in women (n = 96,123; P = 4 × 10(-6)). Additional epigenome-wide methylation analyses using whole blood highlighted 36 differentially methylated sites associated with mLOY...
March 27, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28346042/decreased-expression-of-aldh5a1-predicts-prognosis-in-patients-with-ovarian-cancer
#2
Xun Tian, Yingyan Han, Lan Yu, Bo Luo, Zheng Hu, Xiong Li, Zongyuan Yang, Xin Wang, Wanqiu Huang, Hui Wang, Qinghua Zhang, Ding Ma
Aldehyde dehydrogenase 5 family, member A1 (ALDH5A1) belongs to the superfamily of aldehyde dehydrogenases (ALDHs). However, the prognostic value of ALDH5A1 in ovarian cancer remains unclear. The aim of this study was to explore the relationship between ALDH5A1 and the prognosis of patients with ovarian cancer (OC). We compared the expression of ALDH5A1 in OC to that innormal controls, using GSE40595 profiling data. Tissue microarray analysis was conducted for192 OC patients, 14 adjacent normal ovary tissues, and 2 normal ovary tissues...
March 27, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28345785/nanog-overexpression-and-its-correlation-with-stem-cell-and-differentiation-markers-in-meningiomas-of-different-who-grades
#3
Diana Freitag, Aaron Lawson McLean, Michèle Simon, Arend Koch, Susanne Grube, Jan Walter, Rolf Kalff, Christian Ewald
NANOG, as a key regulator of pluripotency and acting synergistically with other factors, has been described as a crucial transcription factor in various types of cancer. In meningiomas the expression of this marker has not yet been described. With our study, we aimed to identify and localize Nanog and other possible markers of pluripotency, stem cell properties and differentiation in meningioma tissue, to elucidate a possible effect on tumorigenesis. The gene expression levels of NANOG (NANOG1 and NANOGP8), SOX2, OCT4, KLF4, ABCG2, CMYC, MSI1, CD44, NOTCH1, NES, SALL4B, TP53 and EPAS1 were quantitatively examined using RT-qPCR in 33 surgical specimens of low- (WHO grade I) as well as in atypical and anaplastic (WHO grade II/III) meningiomas with dural tissue as reference...
March 27, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28345467/mitochondrial-dna-alteration-in-primary-and-metastatic-colorectal-cancer-different-frequency-and-association-with-selected-clinicopathological-and-molecular-markers
#4
Britta Kleist, Thuja Meurer, Micaela Poetsch
This study attempts to determine whether primary tumor tissue could reliably represent metastatic colorectal cancer in therapy-guiding analysis of mitochondrial microsatellite instability. Therefore, we investigated the concordance of microsatellite instability in D310, D514, and D16184 (mitochondrial DNA displacement loop), and its association with selected clinical categories and KRAS/NRAS/BRAF/PIK3CA/TP53 mutation status between primary and metastatic colorectal cancer tissue from 119 patients. Displacement loop microsatellite instability was significantly more frequently seen in lymph node metastases (53...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28345329/lycopene-extracts-from-different-tomato-based-food-products-induce-apoptosis-in-cultured-human-primary-prostate-cancer-cells-and-regulate-tp53-bax-and-bcl-2-transcript-expression
#5
Nathalia da Costa Pereira Soares, Clara Lima Machado, Bruno Boquimpani Trindade, Ingridy Celestino do Canto Lima, Etel Rodrigues Pereira Gimba, Anderson Junger Teodoro, Christina Takiya, Radovan Borojevic
Carotenoids are the main tomato components, especially lycopene. Lycopene is more bioavailable in tomato processed products than in raw tomatos, since formation of lycopene cis-isomers during food processing and storage may increase its biological activity. In the current study, we evaluated the influence of lycopene extracts (5 mg / mL) from different tomato-based food products (paste, sauce, extract and ketchup) on cell viability and apoptosis on primary human prostate cancer cells (PCa cels) for 96h. Using MTT assay, we observed a significant decrease on primary PCa cell viability upon treatment with lycopene extracted from either 4 tomato-based food products...
February 1, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28344865/identification-of-genetic-determinants-of-breast-cancer-immune-phenotypes-by-integrative-genome-scale-analysis
#6
Wouter Hendrickx, Ines Simeone, Samreen Anjum, Younes Mokrab, François Bertucci, Pascal Finetti, Giuseppe Curigliano, Barbara Seliger, Luigi Cerulo, Sara Tomei, Lucia Gemma Delogu, Cristina Maccalli, Ena Wang, Lance D Miller, Francesco M Marincola, Michele Ceccarelli, Davide Bedognetti
Cancer immunotherapy is revolutionizing the clinical management of several tumors, but has demonstrated limited activity in breast cancer. The development of more effective treatments is hindered by incomplete knowledge of the genetic determinant of immune responsiveness. To fill this gap, we mined copy number alteration, somatic mutation, and expression data from The Cancer Genome Atlas (TCGA). By using RNA-sequencing data from 1,004 breast cancers, we defined distinct immune phenotypes characterized by progressive expression of transcripts previously associated with immune-mediated rejection...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344639/aflatoxin-b1-inhibits-the-type-1-interferon-response-pathway-via-stat1-suggesting-another-mechanism-of-hepatocellular-carcinoma
#7
Patrick W Narkwa, David J Blackbourn, Mohamed Mutocheluh
BACKGROUND: Aflatoxin B1 (AFB1) contamination of food is very high in most sub-Saharan African countries. AFB1 is known to cause hepatocellular carcinoma (HCC) by inducing mutation in the tumour suppressor gene TP53. The number of new HCC cases is high in West Africa with an accompanying high mortality. The type I interferon (IFN) pathway of the innate immune system limits viral infections and exerts its anti-cancer property by up-regulating tumour suppressor activities and pro-apoptotic pathways...
2017: Infectious Agents and Cancer
https://www.readbyqxmd.com/read/28342221/p53-immunohistochemistry-in-high-grade-urothelial-carcinoma-of-the-bladder-is-prognostically-significant
#8
Anjelica Hodgson, Bin Xu, Michelle R Downes
AIMS: TP53 mutations are characteristic of the high grade pathway in the dual pathway of urothelial carcinogenesis. These mutations have been correlated with aberrant accumulation of p53 protein, however the definition and significance of this varies in the literature. We assessed p53 immunostaining in a cohort of high grade urothelial carcinomas using standard published cut offs and a novel binarized method which included assessment of the null phenotype. Each scoring method was correlated with oncologic outcome...
March 25, 2017: Histopathology
https://www.readbyqxmd.com/read/28339894/frequency-of-somatic-tp53-mutations-in-combination-with-known-pathogenic-mutations-as-identified-by-next-generation-sequencing
#9
Zahra Shajani-Yi, Francine De Abreu, Jason Peterson, Gregory Tsongalis
No abstract text is available yet for this article.
March 1, 2017: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28339163/next-generation-sequencing-of-urine-specimens-a-novel-platform-for-genomic-analysis-in-patients-with-non-muscle-invasive-urothelial-carcinoma-treated-with-bacille-calmette-gu%C3%A3-rin
#10
Sasinya N Scott, Irina Ostrovnaya, Caroline M Lin, Nancy Bouvier, Bernard H Bochner, Gopakumar Iyer, David Solit, Michael F Berger, Oscar Lin
BACKGROUND: Biopsies from patients with high-risk (HR) non-muscle-invasive urothelial carcinoma (NMIUC), especially flat urothelial carcinoma in situ, frequently contain scant diagnostic material or denuded mucosa only, and this precludes further extensive genomic analysis. This study evaluated the use of next-generation sequencing (NGS) analysis of urine cytology material from patients with HR NMIUC in an attempt to identify genetic alterations that might correlate with clinical features and responses to bacille Calmette-Guérin (BCG) treatment...
March 24, 2017: Cancer
https://www.readbyqxmd.com/read/28339050/p53-mutation-status-is-a-primary-determinant-of-placenta-specific-protein-1-expression-in-serous-ovarian-cancers
#11
Eric J Devor, Jesus Gonzalez-Bosquet, Akshaya Warrier, Henry D Reyes, Nonye V Ibik, Brandon M Schickling, Andreea Newtson, Michael J Goodheart, Kimberly K Leslie
Placenta-specific protein 1 (PLAC1) expression is co-opted in numerous human cancers. As a consequence of PLAC1 expression, tumor cells exhibit enhanced proliferation and invasiveness. This characteristic is associated with increased aggressiveness and worse patient outcomes. Recently, the presence of the tumor suppressor p53 was shown in vitro to inhibit PLAC1 transcription by compromising the P1, or distal/cancer, promoter. We sought to determine if this phenomenon occurs in primary patient tumors as well...
March 23, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28338653/breast-ductal-carcinoma-in-situ-carry-mutational-driver-events-representative-of-invasive-breast-cancer
#12
Jia-Min B Pang, Peter Savas, Andrew P Fellowes, Gisela Mir Arnau, Tanjina Kader, Ravikiran Vedururu, Chelsee Hewitt, Elena A Takano, David J Byrne, David Yh Choong, Ewan Ka Millar, C Soon Lee, Sandra A O'Toole, Sunil R Lakhani, Margaret C Cummings, G Bruce Mann, Ian G Campbell, Alexander Dobrovic, Sherene Loi, Kylie L Gorringe, Stephen B Fox
The spectrum of genomic alterations in ductal carcinoma in situ (DCIS) is relatively unexplored, but is likely to provide useful insights into its biology, its progression to invasive carcinoma and the risk of recurrence. DCIS (n=20) with a range of phenotypes was assessed by massively parallel sequencing for mutations and copy number alterations and variants validated by Sanger sequencing. PIK3CA mutations were identified in 11/20 (55%), TP53 mutations in 6/20 (30%), and GATA3 mutations in 9/20 (45%). Screening an additional 91 cases for GATA3 mutations identified a final frequency of 27% (30/111), with a high proportion of missense variants (8/30)...
March 24, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28338004/tigar-knockdown-radiosensitizes-trxr1-overexpressing-glioma-in-vitro-and-in-vivo-via-inhibiting-trx1-nuclear-transport
#13
Yushuo Zhang, Fei Chen, Guomei Tai, Jiaojiao Wang, Jun Shang, Bing Zhang, Ping Wang, Baoxing Huang, Jie Du, Jiahua Yu, Haowen Zhang, Fenju Liu
The up-regulation of thioredoxin reductase-1 (TrxR1) is detected in more than half of gliomas, which is significantly associated with increased malignancy grade and recurrence rate. The biological functions of NADPH-dependent TrxR1 are mainly associated with reduced thioredoxin-1 (Trx1) which plays critical roles in cellular redox signaling and tumour radio-resistance. Our previous work has proved that TP53 induced glycolysis and apoptosis regulator (TIGAR) knockdown could notably radiosensitize glioma cells...
March 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28336930/tp53-arg72pro-mortality-after-cancer-and-all-cause-mortality-in-105-200-individuals
#14
Jakob B Kodal, Signe Vedel-Krogh, Camilla J Kobylecki, Børge G Nordestgaard, Stig E Bojesen
Rs1042522 (Arg72Pro) is a functional polymorphism of TP53. Pro72 has been associated with lower all-cause mortality and lower mortality after cancer. We hypothesized that TP53 Pro72 is associated with lower mortality after cancer, lower all-cause mortality, and with increased cancer incidence in the general population in a contemporary cohort. We genotyped 105,200 individuals aged 20-100 years from the Copenhagen General Population Study, recruited in 2003-2013, and followed them in Danish health registries...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28335073/clinical-characteristics-and-whole-exome-transcriptome-sequencing-of-coexisting-chronic-myeloid-leukemia-and-myelofibrosis
#15
Malathi Kandarpa, Yi-Mi Wu, Dan Robinson, Patrick William Burke, Arul M Chinnaiyan, Moshe Talpaz
Myeloproliferative neoplasms (MPNs) are clonal hematopoietic stem cell (HSC) disorders that can be classified on the basis of genetic, clinical, phenotypic features. Genetic lesions such as JAK2 mutations and BCR-ABL translocation are often mutually exclusive in MPN patients and lead to essential thrombocythemia, polycythemia vera or myelofibrosis (ET/PV/MF) or chronic myeloid leukemia, respectively. Nevertheless, coexistence of these genetic aberrations in the same patient has been reported. Whether these aberrations occur in the same stem cell or a different cell is unclear, but an unstable genome in the HSCs seems to be the common antecedent...
March 23, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28333239/small-bowel-carcinomas-in-coeliac-or-crohn-s-disease-clinico-pathological-molecular-and-prognostic-features-a-study-from-the-small-bowel-cancer-italian-consortium
#16
Alessandro Vanoli, Antonio Di Sabatino, Daniela Furlan, Catherine Klersy, Federica Grillo, Roberto Fiocca, Claudia Mescoli, Massimo Rugge, Gabriella Nesi, Paolo Fociani, Gianluca Sampietro, Sandro Ardizzone, Ombretta Luinetti, Antonio Calabrò, Francesco Tonelli, Umberto Volta, Donatella Santini, Giacomo Caio, Paolo Giuffrida, Luca Elli, Stefano Ferrero, Giovanni Latella, Antonio Ciardi, Roberto Caronna, Gaspare Solina, Aroldo Rizzo, Carolina Ciacci, Francesco P D'Armiento, Marianna Salemme, Vincenzo Villanacci, Renato Cannizzaro, Vincenzo Canzonieri, Luca Reggiani Bonetti, Livia Biancone, Giovanni Monteleone, Augusto Orlandi, Giuseppe Santeusanio, Maria C Macciomei, Renata D'Incà, Vittorio Perfetti, Giancarlo Sandri, Marco Silano, Ada M Florena, Antonino G Giannone, Claudio Papi, Luigi Coppola, Paolo Usai, Antonio Maccioni, Marco Astegiano, Paola Migliora, Rachele Manca, Michele Martino, Davide Trapani, Roberta Cerutti, Paola Alberizzi, Roberta Riboni, Fausto Sessa, Marco Paulli, Enrico Solcia, Gino R Corazza
Background and Aims.: An increased risk of small bowel carcinoma (SBC) has been reported in coeliac disease (CD) and Crohn's disease (CrD). We explored clinico-pathologic, molecular and prognostic features of CD-associated SBC (CD-SBC) and CrD-associated SBC (CrD-SBC) in comparison with sporadic SBC (spo-SBC). Methods.: Seventy-six patients undergoing surgical resection for non-familial SBC (26 CD-SBC, 25 CrD-SBC, 25 spo-SBC) were retrospectively enrolled to investigate patients' survival and histological and molecular features including microsatellite instability (MSI) and KRAS/NRAS, BRAF, PIK3CA, TP53, HER2 gene alterations...
February 24, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/28329645/frequent-somatic-mutations-of-chromatin-remodeling-genes-in-metastatic-cutaneous-squamous-cell-carcinoma
#17
Amanda Ewart Toland
Exome and targeted sequencing studies have identified potential driver mutations for a variety of tumor types. Cutaneous squamous cell carcinoma (cSCC) is one of the most highly mutated cancers but is typically correlated with high survival rates and low rates of metastasis. Nevertheless, metastatic cSCC is a significant health threat; up to 8800 individuals are estimated to die yearly from this disease. As it is difficult to predict which cSCCs are more likely to metastasize, and because there are no targeted therapies specifically designated for metastatic cSCC, we performed exome and targeted sequencing of 18 metastatic and 10 primary cSCCs to identify mutations with potential therapeutic benefit...
September 15, 2016: Dermatology Online Journal
https://www.readbyqxmd.com/read/28327999/comprehensive-genomic-profiling-of-salivary-mucoepidermoid-carcinomas-reveals-frequent-bap1-pik3ca-and-other-actionable-genomic-alterations
#18
K Wang, J D McDermott, A B Schrock, J A Elvin, L Gay, S D Karam, D Raben, H Somerset, S M Ali, J S Ross, D W Bowles
Background: We sought to identify genomic alterations (GAs) in salivary mucoepidermoid carcinomas. Patients and methods: DNA was extracted from 48 mucoepidermoid carcinomas. Comprehensive genomic profiling (CGP) including the calculation to tumor mutational burden (TMB) was performed on hybridization-captured adaptor ligation-based libraries of 315 cancer-related genes plus introns from 28 genes frequently rearranged for cancer and evaluated for all classes of GAs...
January 16, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28327908/predicted-vitamin-d-status-and-colon-cancer-recurrence-and-mortality-in-calgb-89803-alliance
#19
M A Fuchs, C Yuan, K Sato, D Niedzwiecki, X Ye, L B Saltz, R J Mayer, R B Mowat, R Whittom, A Hantel, A Benson, D Atienza, M Messino, H Kindler, A Venook, F Innocenti, R S Warren, M M Bertagnolli, S Ogino, E L Giovannucci, E Horvath, J A Meyerhardt, K Ng
Background: HASH(0x4ca70f0) Observational studies suggest that higher levels of 25-hydroxyvitamin D 3 (25(OH)D) are associated with a reduced risk of colorectal cancer and improved survival of colorectal cancer patients. However, the influence of vitamin D status on cancer recurrence and survival of patients with stage III colon cancer is unknown. Patients and methods: HASH(0x4caaca8) We prospectively examined the influence of post-diagnosis predicted plasma 25(OH)D on outcome among 1,016 patients with stage III colon cancer who were enrolled in a National Cancer Institute-sponsored adjuvant therapy trial (CALGB 89803)...
March 15, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28327601/bcip-a-gene-centered-platform-for-identifying-potential-regulatory-genes-in-breast-cancer
#20
Jiaqi Wu, Shuofeng Hu, Yaowen Chen, Zongcheng Li, Jian Zhang, Hanyu Yuan, Qiang Shi, Ningsheng Shao, Xiaomin Ying
Breast cancer is a disease with high heterogeneity. Many issues on tumorigenesis and progression are still elusive. It is critical to identify genes that play important roles in the progression of tumors, especially for tumors with poor prognosis such as basal-like breast cancer and tumors in very young women. To facilitate the identification of potential regulatory or driver genes, we present the Breast Cancer Integrative Platform (BCIP, http://omics.bmi.ac.cn/bcancer/). BCIP maintains multi-omics data selected with strict quality control and processed with uniform normalization methods, including gene expression profiles from 9,005 tumor and 376 normal tissue samples, copy number variation information from 3,035 tumor samples, microRNA-target interactions, co-expressed genes, KEGG pathways, and mammary tissue-specific gene functional networks...
March 22, 2017: Scientific Reports
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