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Maria Costales, Alejandro López-Hernández, Cristina García-Inclán, Blanca Vivanco, Fernando López, José Luis Llorente, Mario A Hermsen
OBJECTIVE: To identify epigenetic events in intestinal-type sinonasal adenocarcinoma (ITAC) and sinonasal squamous cell carcinoma (SNSCC) and to evaluate their relation to clinicopathologic features and follow-up data. STUDY DESIGN: Retrospective study. SETTING: Academic research hospital. SUBJECTS AND METHODS: The methylation status of 23 genes in 50 ITACs and 32 SNSCCs was analyzed by methylation-specific multiplex ligation-dependent probe amplification and its relation to clinicopathologic features and follow-up data...
June 14, 2016: Otolaryngology—Head and Neck Surgery
Kai Ma, Baoping Cao, Mingzhou Guo
Esophageal cancer is one of the most common malignancies in the world. Squamous cell carcinoma accounts for approximately 90 % of esophageal cancer cases. Genetic and epigenetic changes have been found to accumulate during the development of various cancers, including esophageal squamous carcinoma (ESCC). Tobacco smoking and alcohol consumption are two major risk factors for ESCC, and both tobacco and alcohol were found to induce methylation changes in ESCC. Growing evidence demonstrates that aberrant epigenetic changes play important roles in the multiple-step processes of carcinogenesis and tumor progression...
2016: Clinical Epigenetics
Janek Kibat, Thomas Schirrmann, Matthias J Knape, Saskia Helmsing, Doris Meier, Michael Hust, Christoph Schröder, Daniela Bertinetti, Gerhard Winter, Khalid Pardes, Mia Funk, Andrea Vala, Nathalia Giese, Friedrich W Herberg, Stefan Dübel, Jörg D Hoheisel
Many diagnostic and therapeutic concepts require antibodies of high specificity. Recombinant binder libraries and related selection approaches allow the efficient isolation of antibodies against almost every target of interest. Nevertheless, it cannot be guaranteed that selected antibodies perform well and interact specifically enough with analytes unless an elaborate characterisation is performed. Here, we present an approach to shorten this process by combining the selection of suitable antibodies with the identification of informative target molecules by means of antibody microarrays, thereby reducing the effort of antibody characterisation by concentrating on relevant molecules...
September 25, 2016: New Biotechnology
Berta Luzón-Toro, Marta Bleda, Elena Navarro, Luz García-Alonso, Macarena Ruiz-Ferrer, Ignacio Medina, Marta Martín-Sánchez, Cristina Y Gonzalez, Raquel M Fernández, Ana Torroglosa, Guillermo Antiñolo, Joaquin Dopazo, Salud Borrego
BACKGROUND: The molecular mechanisms leading to sporadic medullary thyroid carcinoma (sMTC) and juvenile papillary thyroid carcinoma (PTC), two rare tumours of the thyroid gland, remain poorly understood. Genetic studies on thyroid carcinomas have been conducted, although just a few loci have been systematically associated. Given the difficulties to obtain single-loci associations, this work expands its scope to the study of epistatic interactions that could help to understand the genetic architecture of complex diseases and explain new heritable components of genetic risk...
2015: BMC Medical Genomics
Lin-Yu Lu, Xiaochun Yu
DNA damage response is required for male fertility. DNA damage repair mediates recombination between homologous chromosomes in meiotic prophase, which is essential for proper chromosome segregation during meiotic division. Interestingly, some DNA damage response proteins are also required for the survival of premeiotic germ cells, but their roles in these cells are still unclear. CHFR was recently shown to participate in DNA damage response, but it remains to be established if CHFR is required for male fertility...
2015: Cell Cycle
Li Gao, Fang Liu, Hui Zhang, Junzhong Sun, Yigai Ma
The CpG island of the promoter region of the checkpoint with fork-head associated and ring finger gene (CHFR), a mitotic checkpoint gene with tumor-suppressor functions, is hypermethylated in various human cancers. The objective of this study was to evaluate the frequency of aberrant CHFR promoter methylation in acute myeloid leukemia (AML) patients in an attempt to improve prognostication. CHFR promoter methylation levels were analyzed in 358 newly diagnosed AML cases and 30 healthy donors by the use of quantitative methylation-specific polymerase chain reaction...
February 2016: Genes, Chromosomes & Cancer
Seth A Brodie, Ge Li, Donald Harvey, Fadlo R Khuri, Paula M Vertino, Johann C Brandes
The mitotic checkpoint protein CHFR has emerged as a major mediator of taxane resistance in cancer. Here we show that CHFR's PAR-binding zinc finger domain (PBZ) mediates a protein interaction with poly-ADP ribosylated PARP1 leading to stabilization of CHFR. Disruption of the CHFR-PARP1 interaction through either PARP1 shRNA-mediated knockdown or overexpression of a PBZ domain peptide induces loss of CHFR protein expression. In an attempt to exploit this observation therapeutically, and to develop compounds with synthetic lethality in combination with taxanes, we performed a high-throughput computational screen of 5,256,508 chemical structures against the published crystal structure of the CHFR PBZ domain to identify candidate small molecule CHFR protein-protein interaction inhibitors...
October 13, 2015: Oncotarget
Zifang Quan, Ni Ye, Zhongxiang Hao, Caifang Wen, Hong Liao, Manli Zhang, Lu Luo, Sanjie Cao, Xintian Wen, Rui Wu, Qigui Yan
The aim of the present study was to investigate the promoter methylation status and mRNA expression of goat tumor‑associated genes, in addition to the mRNA expression of DNA methyltransferase genes in enzootic nasal tumors (ENT). Methylation‑specific polymerase chain reaction and SYBR Green reverse transcription‑quantitative polymerase chain reaction were used to detect the methylation status and the mRNA expression levels of DNA methyltransferases (DNMTs), O6‑methylguanine‑DNA methyltransferase (MGMT), the tumor suppressor genes P73, P53, GADD45G, CHFR and THBS1, the transcription factor CEBPA, the proto‑oncogenes KRAS, NRAS and C‑myc and EGFR in 24 nasal tumor tissue samples and 20 normal nasal epithelia tissue samples...
October 2015: Molecular Medicine Reports
Haiyan Chen, Tingguo Zhang, Yan Sheng, Cheng Zhang, Yunfei Peng, Xiao Wang, Cuijuan Zhang
DNA methylation is considered as a significant mechanism that silences tumor suppressor genes (TSGs) and could be used in the early diagnosis of cancer. Histone modifications often work together with DNA methylation; however, how these epigenetic alterations regulate TSGs remains unclear. Here, we determined the methylation status of ten TSGs (3OST2, ppENK, CHFR, LKB1, THBS1, HIC1, SLIT2, EDNRB, COX2, and CLDN7) in hepatocellular carcinoma (HCC) and corresponding noncancerous tissues. Methylation profiling revealed that four genes had very high frequencies of methylation in HCCs, but interestingly, similar high frequencies were also detected in corresponding noncancerous tissues (97...
2015: Journal of Cancer
Mingzhou Guo, Joshi Alumkal, Tatiana Drachova, Dan Gao, Serban S Marina, Jin Jen, James G Herman
DNA methylation occurs commonly in non-small cell lung cancer (NSCLC). We sought to determine the frequency and relationship of methylation of key genes involved in the pathways of mitotic checkpoint control, DNA damage repair, apoptosis, and growth factor signaling in these patients. We analyzed the DNA methylation status of eight genes (CHFR, FANCF, MGMT, p16, DAPK, ASC or TMS-1, RAR-B, and CRBP1) using nested methylation-specific PCR (MSP) on over 314 paraffin-embedded, human non-small cell lung cancer samples...
March 2015: Discovery Medicine
Tianyang Yun, Yang Liu, Dan Gao, Enqiang Linghu, Malcolm V Brock, Dongtao Yin, Qimin Zhan, James G Herman, Mingzhou Guo
Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies worldwide. Both genetic and epigenetic changes are involved in esophageal carcinogenesis. CHFR methylation has been found frequently in different cancers and is regarded as a marker of taxane sensitivity. CHFR methylation was found in 0% (0/16) of normal mucosa, 2.9% (1/34) of grade I dysplasia, 0% (0/8) of grade II dysplasia, 12.5% (1/8) of grade III dysplasia and 45% (49/109) of invasive cancer. When treated with docetaxel or paclitaxel, cell viability was lower in CHFR methylated esophageal cancer cells than in unmethylated cells (p<0...
January 2015: Genes & Cancer
Aiqin Song, Junli Ye, Kunpeng Zhang, Hongsheng Yu, Yanhua Gao, Hongfang Wang, Lirong Sun, Xiaoming Xing, Kun Yang, Min Zhao
Checkpoint with FHA and Ring Finger (CHFR) is a checkpoint protein that reportedly initiates a cell cycle delay in response to microtubule stress during prophase in mitosis, which has become an interesting target for understanding cancer pathogenesis. Recently, aberrant methylation of the CHFR gene associated with gene silencing has been reported in several cancers. In the present study, we examined the expression of CHFR in B-cell non-Hodgkin lymphoma (B-NHL) in vitro and in vivo. Our results showed that the expression level of CHFR mRNA and protein was reduced in B-NHL tissue samples and B cell lines...
May 2015: Leukemia Research
Rosa Murria, Sarai Palanca, Inmaculada de Juan, Cecilia Egoavil, Cristina Alenda, Zaida García-Casado, María J Juan, Ana B Sánchez, Ana Santaballa, Isabel Chirivella, Ángel Segura, David Hervás, Marta Llop, Eva Barragán, Pascual Bolufer
This study investigates the relationship of promoter methylation in tumor suppressor genes with copy-number aberrations (CNA) and with tumor markers in breast cancer (BCs). The study includes 98 formalin fixed paraffin-embedded BCs in which promoter methylation of 24 tumour suppressor genes were assessed by Methylation-Specific Multiplex Ligation-dependent Probe Amplification (MS-MLPA), CNA of 20 BC related genes by MLPA and ER, PR, HER2, CK5/6, CK18, EGFR, Cadherin-E, P53, Ki-67 and PARP expression by immunohistochemistry (IHC)...
2015: American Journal of Cancer Research
Dominique Perdereau, Katia Cailliau, Edith Browaeys-Poly, Arlette Lescuyer, Nadège Carré, Fadila Benhamed, Diana Goenaga, Anne-Françoise Burnol
Beyond its key role in the control of energy metabolism, insulin is also an important regulator of cell division and neoplasia. However, the molecular events involved in insulin-driven cell proliferation are not fully elucidated. Here, we show that the ubiquitin ligase Chfr, a checkpoint protein involved in G2/M transition, is a new effector involved in the control of insulin-induced cell proliferation. Chfr is identified as a partner of the molecular adapter Grb14, an inhibitor of insulin signalling. Using mammalian cell lines and the Xenopus oocyte as a model of G2/M transition, we demonstrate that Chfr potentiates the inhibitory effect of Grb14 on insulin-induced cell division...
April 2015: Cellular Signalling
Seth A Brodie, Ge Li, Johann C Brandes
BACKGROUND: CHFR expression has previously been established as a powerful predictor for response to taxane based first-line chemotherapy in non-small cell lung cancer. It is currently unknown however, if reduced CHFR expression correlates with certain molecular subtypes of lung cancer. PURPOSE: In order to determine which patients may benefit from CHFR biomarker testing we conducted the present study to characterize clinical and molecular characteristics of patients with reduced vs...
January 2015: Respiratory Medicine
He Guo, Wenji Yan, Yunsheng Yang, Mingzhou Guo
OBJECTIVE: To detect the status of promoter region methylation of damage repair genes in gastric cancer and analyze its association with clinicopathologic characteristics. METHODS: A total of 70 human gastric cancer tissue samples representing all stages of disease were obtained from surgical resection specimens. DNA was extracted with the phenol-chloroform method. The technique of methylation specific polymerase chain reaction (MSP) was used to examine the methylation status of MLH1, CHFR, MGMT, FANCF, Rassf1A, BRCA1 and GSTpi in gastric cancer specimens...
July 22, 2014: Zhonghua Yi Xue za Zhi [Chinese medical journal]
Rob Noorlag, Pauline M W van Kempen, Cathy B Moelans, Rick de Jong, Laura E R Blok, Ronald Koole, Wilko Grolman, Paul J van Diest, Robert J J van Es, Stefan M Willems
Silencing of tumor suppressor genes (TSGs) by DNA promoter hypermethylation is an early event in carcinogenesis and a potential target for personalized cancer treatment. In head and neck cancer, little is known about the role of promoter hypermethylation in survival. Using methylation specific multiplex ligation-dependent probe amplification (MS-MLPA) we investigated the role of promoter hypermethylation of 24 well-described genes (some of which are classic TSGs), which are frequently methylated in different cancer types, in 166 HPV-negative early oral squamous cell carcinomas (OSCC), and 51 HPV-negative early oropharyngeal squamous cell carcinomas (OPSCC) in relation to clinicopathological features and survival...
September 2014: Epigenetics: Official Journal of the DNA Methylation Society
Kouji Banno, Megumi Yanokura, Miho Iida, Kenta Masuda, Daisuke Aoki
Endometrial cancer is increasing worldwide and the number of patients with this disease is likely to continue to grow, including younger patients. Many endometrial cancers show estrogen-dependent proliferation, but the carcinogenic mechanisms are unknown or not completely explained beyond mutations of single oncogenes and tumor suppressor genes. Possible carcinogenic mechanisms include imbalance between endometrial proliferation by unopposed estrogen and the mismatch repair (MMR) system; hypermethylation of the MMR gene hMLH1; mutation of PTEN, β-catenin and K-ras genes in type I endometrial cancer and of HER-2/neu and p53 genes in type II endometrial cancer; hypermethylation of SPRY2, RASSF1A, RSK4, CHFR and CDH1; and methylation of tumor suppressor microRNAs, including miR-124, miR-126, miR-137, miR-491, miR-129-2 and miR-152...
August 2014: Journal of Obstetrics and Gynaecology Research
Pauline M W van Kempen, Liselotte van Bockel, Weibel W Braunius, Cathy B Moelans, Marina van Olst, Rick de Jong, Inge Stegeman, Paul J van Diest, Wilko Grolman, Stefan M Willems
Oropharyngeal squamous cell carcinoma (OPSCC) is associated with human papillomavirus (HPV) in a proportion of tumors. HPV-positive OPSCC is considered a distinct molecular entity with a prognostic advantage compared to HPV-negative cases. Silencing of cancer-related genes by DNA promoter hypermethylation may play an important role in the development of OPSCC. Hence, we examined promoter methylation status in 24 common tumor suppressor genes in a group of 200 OPSCCs to determine differentially methylated genes in HPV-positive versus HPV-negative primary OPSCC...
October 2014: Cancer Medicine
K J Leong, A Beggs, J James, D G Morton, G M Matthews, S P Bach
BACKGROUND: Total mesorectal excision (TME) remains commonplace for T1-2 rectal cancer owing to fear of undertreating a small proportion of patients with node-positive disease. Molecular stratification may predict cancer progression. It could be used to select patients for organ-preserving surgery if specific biomarkers were validated. METHODS: Gene methylation was quantified using bisulphite pyrosequencing in 133 unirradiated rectal cancer TME specimens. KRAS mutation and microsatellite instability status were also defined...
September 2014: British Journal of Surgery
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