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https://www.readbyqxmd.com/read/28108518/a-transposon-based-analysis-reveals-rasa1-is-involved-in-triple-negative-breast-cancer
#1
Cristian Suárez-Cabrera, Rita M Quintana, Ana Bravo, M LLanos Casanova, Angustias Page, Josefa P Alameda, Jesus M Paramio, Alicia Maroto, Javier Salamanca, Adam J Dupuy, Angel Ramírez, Manuel Navarro
RAS genes are mutated in 20% of human tumors, but these mutations are very rare in breast cancer. Here we used a mouse model to generate tumors upon activation of a mutagenic T2Onc2 transposon via expression of a transposase driven by the keratin K5 promoter in a p53+/- background. These animals mainly developed mammary tumors, most of which had transposon insertions in one of two RASGAP genes, neurofibromin1 (NF1) and RAS p21 protein activator (Rasa1). Immunohistochemical analysis of a collection of human breast tumors confirmed that low expression of RASA1 is frequent in basal (triple-negative) and ER-negative tumors...
January 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28108243/tpx2-as-a-prognostic-indicator-and-potential-therapeutic-target-in-clear-cell-renal-cell-carcinoma
#2
Zachary A Glaser, Harold D Love, Shunhua Guo, Lan Gellert, Sam S Chang, Stanley Duke Herrell, Daniel A Barocas, David F Penson, Michael S Cookson, Peter E Clark
OBJECTIVES: Our aims were to determine if targeting protein for Xklp2 (TPX2) is correlated with clear cell renal cell carcinoma (ccRCC) histology and oncologic outcomes using The Cancer Genome Atlas (TCGA) and an institutional tissue microarray (TMA). METHODS: Clinicopathological data obtained from the TCGA consisted of 415 samples diagnosed with ccRCC. A TMA was constructed from tumors of 207 patients who underwent radical nephrectomy for ccRCC. TPX2 expression by immunohistochemistry on TMA was assessed by a genitourinary pathologist...
January 17, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28107606/dishevelled-segment-polarity-protein-3-dvl3-a-novel-and-easily-applicable-recurrence-predictor-in-localized-prostate-adenocarcinoma
#3
Pil-Jong Kim, Ji Y Park, Hong-Gee Kim, Yong Mee Cho, Heounjeong Go
OBJECTIVE: To identify new biomarkers for the biochemical recurrence (BCR) of prostate adenocarcinoma. PATIENTS AND METHODS: Clinical information of 500 prostate adenocarcinoma patients and their 152 RNA-sequencing and protein-array data from The Cancer Genome Atlas (TCGA) were separated into a discovery-set and a validation-set. Each dataset was analyzed according to the Gleason grade groups reflecting BCR. The results obtained from the analysis using TCGA dataset were confirmed by immunohistochemistry analyses of the confirmation cohort composed of 395 localized prostate adenocarcinoma patients...
January 20, 2017: BJU International
https://www.readbyqxmd.com/read/28105922/differential-expression-of-alternatively-spliced-transcripts-related-to-energy-metabolism-in-colorectal-cancer
#4
Anastasiya Vladimirovna Snezhkina, George Sergeevich Krasnov, Andrew Rostislavovich Zaretsky, Alex Zhavoronkov, Kirill Mikhailovich Nyushko, Alexey Alexandrovich Moskalev, Irina Yurievna Karpova, Anastasiya Isaevna Afremova, Anastasiya Valerievna Lipatova, Dmitriy Vladimitovich Kochetkov, Maria Sergeena Fedorova, Nadezhda Nikolaevna Volchenko, Asiya Fayazovna Sadritdinova, Nataliya Vladimirovna Melnikova, Dmitry Vladimirovich Sidorov, Anatoly Yurievich Popov, Dmitry Valerievich Kalinin, Andrey Dmitrievich Kaprin, Boris Yakovlevich Alekseev, Alexey Alexandrovich Dmitriev, Anna Viktorovna Kudryavtseva
BACKGROUND: Colorectal cancer (CRC) is one of the most common malignant tumors worldwide. CRC molecular pathogenesis is heterogeneous and may be followed by mutations in oncogenes and tumor suppressor genes, chromosomal and microsatellite instability, alternative splicing alterations, hypermethylation of CpG islands, oxidative stress, impairment of different signaling pathways and energy metabolism. In the present work, we have studied the alterations of alternative splicing patterns of genes related to energy metabolism in CRC...
December 28, 2016: BMC Genomics
https://www.readbyqxmd.com/read/28104536/exome-wide-association-study-identifies-low-frequency-coding-variants-in-2p23-2-and-7p11-2-associated-with-survival-of-non-small-cell-lung-cancer-patients
#5
Meng Zhu, Liguo Geng, Wei Shen, Yuzhuo Wang, Jia Liu, Yang Cheng, Cheng Wang, Juncheng Dai, Guangfu Jin, Zhibin Hu, Hongxia Ma, Hongbing Shen
INTRODUCTION: A growing body of evidence has suggested that low-frequency or rare variants might have strong effects on the development and prognosis of cancer. Here, we aim to assess the role of low-frequency and rare coding variants in the survival of non-small cell lung cancer (NSCLC) in Chinese populations. METHODS: We performed an exome-wide scan of 247,870 variants in 1,008 NSCLC patients and replicated the promising variants by using imputed genotype data of The Cancer Genome Atlas (TCGA) with a cox regression model...
January 16, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28102032/nonpromoter-methylation-of-the-cdkn2a-gene-with-active-transcription-is-associated-with-improved-locoregional-control-in-laryngeal-squamous-cell-carcinoma
#6
Miriam M Ben-Dayan, Thomas J Ow, Thomas J Belbin, Joshua Wetzler, Richard V Smith, Geoffrey Childs, Brenda Diergaarde, D Neil Hayes, Jennifer R Grandis, Michael B Prystowsky, Nicolas F Schlecht
We previously reported a novel association between CDKN2A nonpromoter methylation and transcription (ARF/INK4a) in human papillomavirus associated oropharyngeal tumors. In this study we assessed whether nonpromoter CDKN2A methylation in laryngeal squamous cell carcinomas (LXSCC) conferred a similar association with transcription that predicted patient outcome. We compared DNA methylation and ARF/INK4a RNA expression levels for the CDKN2A locus using the Illumina HumanMethylation27 beadchip and RT-PCR in 43 LXSCC tumor samples collected from a prospective study of head and neck cancer patients treated at Montefiore Medical Center (MMC)...
January 19, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28101574/nek2-serves-as-a-prognostic-biomarker-for-hepatocellular-carcinoma
#7
Gang Li, Yanping Zhong, Qingrong Shen, Yi Zhou, Xiaofang Deng, Cuiping Li, Jiagui Chen, Ying Zhou, Min He
Never in mitosis gene A (NIMA)-related kinase 2 (NEK2) is a microtubule-associated protein that regulates spindle assembly in human cells and is overexpressed in various malignancies. However, the role of NEK2 in hepatocellular carcinoma (HCC) remains undetermined. We performed RNA-seq of the HCC cell line SMMC-7721 and the normal liver cell line HL-7702 using the Ion Proton System. NEK2 expression was detected using quantitative reverse transcription polymerase chain reaction in two cell lines and 5 matched HCC and adjacent non-tumorous liver tissues...
February 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28100567/mecp2-regulated-glycogenes-contribute-to-proliferation-and-apoptosis-of-gastric-cancer-cells
#8
Yannan Qin, Lingyu Zhao, Xiaofei Wang, Dongdong Tong, Christopher Hoover, Fei Wu, Yingxun Liu, Lumin Wang, Liying Liu, Lei Ni, Tusheng Song, Chen Huang
Aberrant glycogene and glycan expression is intimately associated with carcinogenesis, invasion, and metastasis of gastric cancer (GC); however the regulatory mechanisms for glycogenes in GC cells remain unclear. Methyl-CpG-binding protein 2 (MeCP2) regulates genes by binding to methylated promoters, and in our previous work we found that it is overexpressed in GC cell lines and tissues, functioning as an oncogene. In this study we detected the expression of 212 glycogenes in MeCP2 silenced GC cells versus control using the Agilent Whole Human Genome Microarray and mining the data through bioinformatic analysis...
January 18, 2017: Glycobiology
https://www.readbyqxmd.com/read/28096648/identification-of-genetic-and-epigenetic-variants-associated-with-breast-cancer-prognosis-by-integrative-bioinformatics-analysis
#9
Arunima Shilpi, Yingtao Bi, Segun Jung, Samir K Patra, Ramana V Davuluri
INTRODUCTION: Breast cancer being a multifaceted disease constitutes a wide spectrum of histological and molecular variability in tumors. However, the task for the identification of these variances is complicated by the interplay between inherited genetic and epigenetic aberrations. Therefore, this study provides an extrapolate outlook to the sinister partnership between DNA methylation and single-nucleotide polymorphisms (SNPs) in relevance to the identification of prognostic markers in breast cancer...
2017: Cancer Informatics
https://www.readbyqxmd.com/read/28092680/utilizing-somatic-mutation-data-from-numerous-studies-for-cancer-research-proof-of-concept-and-applications
#10
D Amar, S Izraeli, R Shamir
Large cancer projects measure somatic mutations in thousands of samples, gradually assembling a catalog of recurring mutations in cancer. Many methods analyze these data jointly with auxiliary information with the aim of identifying subtype-specific results. Here, we show that somatic gene mutations alone can reliably and specifically predict cancer subtypes. Interpretation of the classifiers provides useful insights for several biomedical applications. We analyze the COSMIC database, which collects somatic mutations from The Cancer Genome Atlas (TCGA) as well as from many smaller scale studies...
January 16, 2017: Oncogene
https://www.readbyqxmd.com/read/28092569/discovery-of-micrornas-and-transcription-factors-co-regulatory-modules-by-integrating-multiple-types-of-genomic-data
#11
Jiawei Luo, Gen Xiang, Chu Pan
It is well known that regulators known as microRNA (miRNA) and transcription factor (TF) have been found to play an important role in gene regulation. However, there are few researches of collaborative regulatory (co-regulatory) mechanism between miRNA and TF on system level (function level). Meanwhile, recent advances in high-throughput genomic technologies have enabled researchers to collect diverse large-scale genomic data, which can be used to study the co-regulatory mechanism between miRNA and TF. In this paper, we propose a novel method called SNCoNMF (Sparse Network regularized non-negative matrix factorization for Co-regulatory modules identification) which adopts multiple non-negative matrix factorization framework to identify co-regulatory modules including miRNAs, TFs and genes...
January 9, 2017: IEEE Transactions on Nanobioscience
https://www.readbyqxmd.com/read/28086747/microrna-based-pan-cancer-diagnosis-and-treatment-recommendation
#12
Nikhil Cheerla, Olivier Gevaert
BACKGROUND: The current state-of-the-art in cancer diagnosis and treatment is not ideal; diagnostic tests are accurate but invasive, and treatments are "one-size fits-all" instead of being personalized. Recently, miRNA's have garnered significant attention as cancer biomarkers, owing to their ease of access (circulating miRNA in the blood) and stability. There have been many studies showing the effectiveness of miRNA data in diagnosing specific cancer types, but few studies explore the role of miRNA in predicting treatment outcome...
January 13, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28079712/a-comprehensive-review-of-genomics-and-noncoding-rna-in-gliomas
#13
Ahmed Hassan, Jennifer Mosley, Sanjay Singh, Pascal Olivier Zinn
Glioblastoma (GBM) is the most malignant primary adult brain tumor. In spite of our greater understanding of the biology of GBMs, clinical outcome of GBM patients remains poor, as their median survival with best available treatment is 12 to 18 months. Recent efforts of The Cancer Genome Atlas (TCGA) have subgrouped patients into 4 molecular/transcriptional subgroups: proneural, neural, classical, and mesenchymal. Continuing efforts are underway to provide a comprehensive map of the heterogeneous makeup of GBM to include noncoding transcripts, genetic mutations, and their associations to clinical outcome...
January 11, 2017: Topics in Magnetic Resonance Imaging: TMRI
https://www.readbyqxmd.com/read/28079598/interobserver-agreement-in-endometrial-carcinoma-histotype-diagnosis-varies-depending-on-the-cancer-genome-atlas-tcga-based-molecular-subgroup
#14
Lien N Hoang, Mary A Kinloch, Joyce M Leo, Katherine Grondin, Cheng-Han Lee, Carol Ewanowich, Martin Köbel, Angela Cheng, Aline Talhouk, Melissa McConechy, David G Huntsman, Jessica N McAlpine, Robert A Soslow, C Blake Gilks
The Cancer Genome Atlas recently identified a genomic-based molecular classification of endometrial carcinomas, with 4 molecular categories: (1) ultramutated (polymerase epsilon [POLE] mutated), (2) hypermutated (microsatellite instability), (3) copy number abnormalities-low, and (4) copy number abnormalities-high. Two studies have since proposed models to classify endometrial carcinomas into 4 molecular subgroups, modeled after The Cancer Genome Atlas, using simplified and more clinically applicable surrogate methodologies...
February 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28077784/identification-and-characterization-of-hpv-independent-cervical-cancers
#15
Carolyn E Banister, Changlong Liu, Lucia Pirisi, Kim E Creek, Phillip J Buckhaults
BACKGROUND: Human papillomavirus (HPV) initiates cervical cancer, and continuous expression of HPV oncogenes E6 and E7 is thought to be necessary to maintain malignant growth. Current therapies target proliferating cells, rather than specific pathways, and most experimental therapies specifically target E6/E7. We investigated the presence and expression of HPV in cervical cancer, to correlate HPV oncogene expression with clinical and molecular features of these tumors that may be relevant to new targeted therapies...
January 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28075458/silencing-of-forkhead-box-d1-inhibits-proliferation-and-migration-in-glioma-cells
#16
Yuan-Feng Gao, Tao Zhu, Xiao-Yuan Mao, Chen-Xue Mao, Ling Li, Ji-Ye Yin, Hong-Hao Zhou, Zhao-Qian Liu
Despite the extensive role of Forkhead box transcription factors in the development and progression of various cancers, little is known about their role in glioma. We examined the expression and function of Forkhead box D1 (FOXD1) in glioma cell behavior and found that FOXD1 was upregulated and directly correlated with the glioma grade. Data analysis also revealed significant differences in FOXD1 expression for both gene expression profiles (GSE4290 and GSE7696) and the TCGA datasets. Additionally, decreased FOXD1 expression in U251 and U87 glioma cells caused a delay in cell growth and a disruption in colony formation...
February 2017: Oncology Reports
https://www.readbyqxmd.com/read/28073773/long-term-survival-and-clinical-benefit-from-adoptive-t-cell-transfer-in-stage-iv-melanoma-patients-is-determined-by-a-four-parameter-tumor-immune-signature
#17
Sara M Melief, Valeria V Visconti, Marten Visser, Merel van Diepen, Ellen H W Kapiteijn, Joost H van den Berg, John B A G Haanen, Vincent T H B M Smit, Jan Oosting, Sjoerd H van der Burg, Els M E Verdegaal
The presence of tumor-infiltrating immune cells is associated with longer survival and a better response to immunotherapy in early-stage melanoma, but a comprehensive study of the in situ immune microenvironment in stage IV melanoma has not been performed. We investigated the combined influence of a series of immune factors on survival and response to adoptive cell transfer (ACT) in stage IV melanoma patients. Metastases of 73 stage IV melanoma patients, 17 of which were treated with ACT, were studied with respect to the number and functional phenotype of lymphocytes and myeloid cells as well as for expression of galectins-1, -3, and -9...
January 10, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28073598/hdac10-as-a-potential-therapeutic-target-in-ovarian-cancer
#18
Muhtadi M Islam, Tapahsama Banerjee, Colin Z Packard, Shweta Kotian, Karuppaiyah Selvendiran, David E Cohn, Jeffrey D Parvin
OBJECTIVE: We analyzed histone deacetylase 10 (HDAC10) for function in the context of the DNA damage response in BRCA1-null ovarian cancer cells as well as evaluated the potential of general HDAC inhibitors in primary ovarian carcinoma cells. HDAC10 had previously been shown to be highly stimulatory to the process of homology directed repair in HeLa cells, and in this study we investigated whether HDAC10 could impact in vitro the response to anticancer therapies. We hypothesized that the loss of HDAC10 would sensitize cells to platinum therapy...
January 7, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28073171/pan-cancer-survey-of-epithelial-mesenchymal-transition-markers-across-the-cancer-genome-atlas
#19
Don L Gibbons, Chad J Creighton
BACKGROUND: While epithelial-mesenchymal transition (EMT) can be readily induced experimentally in cancer cells, the EMT process as manifested in human tumors needs to be better understood. Pan-cancer genomic datasets from The Cancer Genome Atlas (TCGA)-representing over 10,000 patients and 32 distinct cancer types-provide a rich resource for examining correlative patterns involving EMT mediators in the setting of human cancers. RESULTS: Here, we surveyed a 16-gene signature of canonical EMT markers in TCGA pan-cancer cohort...
January 10, 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/28070553/predicted-neoantigen-load-in-non-hypermutated-endometrial-cancers-correlation-with-outcome-and-tumor-specific-genomic-alterations
#20
Sachet A Shukla, Brooke E Howitt, Catherine J Wu, Panagiotis A Konstantinopoulos
Elevated neoantigen load has been previously correlated with improved outcome and response to immune checkpoint blockade in various tumor types. In endometrial cancer, previous studies of neoantigen load prediction have shown that the hypermutated MSI and POLE-mutated tumors harbor significantly higher predicted neoantigen load compared to the hypomutated CN-low/endometrioid and CN-high/serous-like tumors. Here, we report that predicted neoantigen load may be a prognostic factor in hypomutated endometrial cancers, both in CN-low/endometrioid and CN-high/serous-like tumors...
February 2017: Gynecologic Oncology Reports
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