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https://www.readbyqxmd.com/read/28522256/sporadic-early-onset-diffuse-gastric-cancers-have-high-frequency-of-somatic-cdh1-alterations-but-low-frequency-of-somatic-rhoa-mutations-compared-with-late-onset-cancers
#1
Soo Young Cho, Jun Won Park, Yang Liu, Young Soo Park, Ju Hee Kim, Hanna Yang, Hyejin Um, Woo Ri Ko, Byung Il Lee, Sun Young Kwon, Seung Wan Ryu, Chae Hwa Kwon, Do Youn Park, Jae-Hyuk Lee, Sang Il Lee, Kyu Sang Song, Hoon Hur, Sang-Uk Han, Heekyung Chang, Su-Jin Kim, Byung-Sik Kim, Jeong-Hwan Yook, Moon-Won Yoo, Beom-Su Kim, In-Seob Lee, Myeong-Cherl Kook, Nina Thiessen, An He, Chip Stewart, Andrew Dunford, Jaegil Kim, Juliann Shih, Gordon Saksena, Andrew D Cherniack, Steven Schumacher, Amaro-Taylor Weiner, Mara Rosenberg, Gad Getz, Eun Gyeong Yang, Min Hee Ryu, Adam J Bass, Hark Kyun Kim
BACKGROUND & AIMS: Early-onset gastric cancer, which develops in younger patients than most gastric cancers, is usually detected at advanced stages, has diffuse histologic features, and occurs more frequently in women. We investigated somatic genomic alterations associated with the unique characteristics of sporadic diffuse gastric cancers (DGCs) from younger patients. METHODS: We conducted whole exome and RNA sequence analyses of 80 resected DGC samples from patients 45 years old or younger in Korea...
May 15, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28521468/poor-prognosis-in-cholangiocarcinoma-patients-with-low-fbxw7-expression-is-improved-by-chemotherapy
#2
Norihiro Ishii, Kenichiro Araki, Takehiko Yokobori, Akira Watanabe, Mariko Tsukagoshi, Norio Kubo, Hideki Suzuki, Fumiyoshi Saito, Bolag Altan, Yasuo Hosouchi, Ken Shirabe, Hiroyuki Kuwano
The tumor suppressor FBXW7 has been demonstrated to degrade several oncoproteins, including c-Myc. Although low FBXW7 expression levels are suggested to be a poor prognostic factor in a number of types of solid tumor, the role of FBXW7 in chemosensitivity is controversial. The purpose of the present study was to determine whether FBXW7 expression may be used as a marker for poor prognosis and chemosensitivity in patients with cholangiocarcinoma (CC). FBXW7 expression was investigated by immunohistochemistry in 100 surgically resected CC samples, and the association between FBXW7 expression, clinicopathological factors and prognosis was evaluated...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28512245/merkel-cell-polyomavirus-small-t-antigen-initiates-merkel-cell-carcinoma-like-tumor-development-in-mice
#3
Monique E Verhaegen, Doris Mangelberger, Paul W Harms, Markus Eberl, Dawn M Wilbert, Julia Meireles, Christopher K Bichakjian, Thomas L Saunders, Sunny Y Wong, Andrzej A Dlugosz
Merkel cell carcinoma (MCC) tumor cells express several markers detected in normal Merkel cells, a non-proliferative population of neuroendocrine cells which arise from epidermis. MCCs frequently contain Merkel cell polyomavirus (MCPyV) DNA and express viral transforming antigens, sT and tLT, but the role of these putative oncogenes in MCC development, and this tumor's cell of origin, are unknown. Using a panel of pre-term transgenic mice, we show that epidermis-targeted co-expression of sT and the cell fate determinant atonal bHLH transcription factor 1 (Atoh1) leads to development of widespread cellular aggregates with histology and marker expression mimicking that of human intraepidermal MCC...
May 16, 2017: Cancer Research
https://www.readbyqxmd.com/read/28507201/sensitivity-of-non-small-cell-lung-cancer-to-erlotinib-is-regulated-by-the-notch-mir-223-fbxw7-pathway
#4
Haiwei Zhang, Fanglin Chen, Yongpeng He, Lin Yi, Chuang Ge, Xiaolong Shi, Chao Tang, Donglin Wang, Yongzhong Wu, Weiqi Nian
Recent evidence supports a role for microRNA-223 (miR-223) in modulating tumor cell sensitivity to chemotherapeutic drugs; however, its role in cellular resistance to the effects of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) used in treatment of non-small cell lung cancer (NSCLC) remains to be elucidated. The levels of miR-223 in parental cell line (HCC827) and erlotinib resistant HCC827 cell line (HCC827/ER)  were detected by qRT-PCR. HCC827/ER cells were treated with MK-2206 to block the Akt signaling pathway or RO4929097 to block the Notch signaling pathway, and then transfected with a miR-223 inhibitor or interference expression plasmid of F-Box/WD repeat-containing protein 7 (FBXW7) or insulin-like growth factor 1 receptor (IGF1R)...
May 15, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28498285/c-myc-and-its-main-ubiquitin-ligase-fbxw7-influence-cell-proliferation-and-prognosis-in-adult-t-cell-leukemia-lymphoma
#5
Yasuhito Mihashi, Mikio Mizoguchi, Yasushi Takamatsu, Kenji Ishitsuka, Hiromi Iwasaki, Monji Koga, Kazunori Urabe, Seiya Momosaki, Toshifumi Sakata, Fumiaki Kiyomi, Morishige Takeshita
Smoldering-type and chronic-type adult T-cell leukemia/lymphomas (ATLL) patients have relatively indolent clinical courses, but often progress into aggressive lymphoma-type and acute-type disease. We examined the roles of transcription factor C-MYC and its ubiquitin ligase FBXW7 in tumor tissues from 137 patients with ATLL. Immunohistochemical tests showed ≥50% of lymphoma cells in 78.7% (48/61) of lymphoma-type, and 64.9% (24/37) of acute-type samples expressed C-MYC, significantly higher than was seen in smoldering-type (3...
May 11, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28487787/ebv-negative-monomorphic-b-cell-posttransplant-lymphoproliferative-disorder-with-marked-morphologic-pleomorphism-and-pathogenic-mutations-in-asxl1-bcor-cdkn2a-nf1-and-tp53
#6
Agata M Bogusz
Posttransplant lymphoproliferative disorders (PTLDs) are a diverse group of lymphoid or plasmacytic proliferations frequently driven by Epstein-Barr virus (EBV). EBV-negative PTLDs appear to represent a distinct entity. This report describes an unusual case of a 33-year-old woman that developed a monomorphic EBV-negative PTLD consistent with diffuse large B-cell lymphoma (DLBCL) 13 years after heart-lung transplant. Histological examination revealed marked pleomorphism of the malignant cells including nodular areas reminiscent of classical Hodgkin lymphoma (cHL) with abundant large, bizarre Hodgkin-like cells...
2017: Case Reports in Hematology
https://www.readbyqxmd.com/read/28464881/fbxw7-expression-is-associated-with-prognosis-and-chemotherapeutic-outcome-in-chinese-patients-with-gastric-adenocarcinoma
#7
Mao-Ran Li, Chun-Chao Zhu, Tian-Long Ling, Ye-Qian Zhang, Jia Xu, En-Hao Zhao, Gang Zhao
BACKGROUND: FBXW7, a component of the Skp-Cullin1-F-box, mediates target protein recognition. It is a tumor suppressor gene that plays a role in the regulation of cell cycle exit and reentry via c-Myc, c-Jun and Notch degradation. There are few studies, particularly involving a large patient cohort, that have evaluated FBXW7 during gastric cancer progression. METHODS: Our study aimed to evaluate the value of FBXW7 as a clinical marker in gastric adenocarcinoma (GC) patients including a subset treated with postoperative chemotherapy...
May 2, 2017: BMC Gastroenterology
https://www.readbyqxmd.com/read/28459460/magea1-interacts-with-fbxw7-and-regulates-ubiquitin-ligase-mediated-turnover-of-nicd1-in-breast-and-ovarian-cancer-cells
#8
J Zhao, Y Wang, C Mu, Y Xu, J Sang
Melanoma-associated antigen A1 (MAGEA1) is member of the MAGE gene family that is expressed in male germ line cells and placenta under normal physiological conditions. Although MAGEA1's expression levels have been evaluated as one of the cancer testis (CT) antigens for immunotherapy in melanoma and several other cancers, its functional role and signaling mechanisms are largely unknown. In this study, we examined the functional involvement and signaling mechanisms of MAGEA1 in breast and ovarian cancer cells...
May 1, 2017: Oncogene
https://www.readbyqxmd.com/read/28447036/recent-translational-research-into-targeted-therapy-for-liposarcoma
#9
REVIEW
Rashi Bharat Patel, Ting Li, Zhichao Liao, Jivani Aakash Jaldeepbhai, H A Pavanika N V Perera, Sujani Kaushalya Muthukuda, Dholiya Hardeep Dhirubhai, Vaibhav Singh, Xiaoling Du, Jilong Yang
Liposarcomas (LPS) are among the most common soft tissue sarcomas, originating from adipocytes. Treatment for LPS typically involves surgical resection and radiation therapy, while the use of conventional cytotoxic chemotherapy for unresectable or metastatic LPS remains controversial. This review summarizes the results of recent translational research and trials of novel therapies targeting various genetic and molecular aberrations in different subtypes of LPS. Genetic aberrations such as the 12q13-15 amplicon, genetic amplification of MDM2, CDK4, TOP2A, PTK7, and CHEK1, point mutations in CTNNB1, CDH1, FBXW7, and EPHA1, as the fusion of FUS-DDIT3/EWSR1-DDIT3 are involved in the pathogenesis LPS and represent potential therapeutic candidates...
2017: Stem Cell Investigation
https://www.readbyqxmd.com/read/28446316/-prognostic-value-of-recurrent-molecular-genetics-and-epigenetics-abnormity-in-t-lymphoblastic-lymphoma-leukemia-review
#10
Wei Guan, Yu Jing, Li Yu
T lymphoblastic lymphoma / leukemia is a strong invasive and has a high incidence of various molecular genetic abnormalities. The NOTCH1 / FBXW7 mutation is one of the most common mutations, and related with good prognosis in T-LBL / ALL. PTEN mutation, a poor prognostic factor, could be overcome by NOTCH1 mutations in pediatric patients to some extent. Patients with MLL gene abnormality and loss of heterozygosity 6q have worse prognosis than those with normal karyotype. The incidence of MLL gene abnormality, RUNX1 mutation and DNMT3A mutation in early precursor T-lymphoblastic leukemia was higher than that of other mature subtypes, which could be used as risk stratification factors...
April 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28442573/cell-cycle-dependent-degradation-of-the-methyltransferase-setd3-attenuates-cell-proliferation-and-liver-tumorigenesis
#11
Xiaoqing Cheng, Yuan Hao, Wenjie Shu, Mengjie Zhao, Chen Zhao, Yuan Wu, Xiaodan Peng, Pinfang Yao, Daibiao Xiao, Guoliang Qing, Zhengying Pan, Lei Yin, Desheng Hu, Hai-Ning Du
Histone modifications, including lysine methylation, are epigenetic marks that influence many biological pathways. Accordingly, many methyltransferases have critical roles in various biological processes, and their dysregulation is often associated with cancer. However, the biological functions and regulation of many methyltransferases are unclear. Here, we report that a human homolog of the methyltransferase SET domain containing 3 (SETD3) is cell cycle regulated: SETD3 protein levels peaked in S phase and were lowest in M phase...
April 25, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28424412/fbxw7-missense-mutation-a-novel-negative-prognostic-factor-in-metastatic-colorectal-adenocarcinoma
#12
Krittiya Korphaisarn, Van Karlyle Morris, Michael J Overman, David R Fogelman, Bryan K Kee, Kanwal Pratap Singh Raghav, Shanequa Manuel, Imad Shureiqi, Robert A Wolff, Cathy Eng, David Menter, Stanley R Hamilton, Scott Kopetz, Arvind Dasari
BACKGROUND: FBXW7 functions as a ubiquitin ligase tagging multiple dominant oncogenic proteins and commonly mutates in colorectal cancer. Data suggest missense mutations lead to greater loss of FBXW7 function than other gene aberrations do. However, the clinicopathologic factors and outcomes associated with FBXW7 missense mutations in metastatic colorectal cancer (mCRC) have not been described. METHODS: Data were obtained from mCRC patients whose tumors were evaluated by next-generation sequencing for hotspot mutations at The University of Texas MD Anderson Cancer Center...
April 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423622/hnrnpk-mir-223-fbxw7-feedback-cascade-promotes-pancreatic-cancer-cell-growth-and-invasion
#13
D He, Cheng Huang, Qingxin Zhou, Dawei Liu, Longhui Xiong, Hongxia Xiang, Guangnian Ma, Zhiyong Zhang
Several studies have identified miR-223 critically involved in various types of cancer, including pancreatic ductal adenocarcinoma (PDAC). However, its action and regulatory mechanisms in PDAC remains largely unclear. In this study, we found that the expression levels of miR-223 were increased in clinical samples with PDAC (81.6%). The upregulation of miR-223 increases the proliferation, migration, and invasive abilities of PDAC cells in vitro and in vivo. Mechanistically, miR-223 directly targeted FBXW7 and overexpression of FBXW7 reverted miR-223- induced drastic proliferation in PDAC cells...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28422719/fbxw7-haploinsufficiency-loses-its-protection-against-dna-damage-and-accelerates-mnu-induced-gastric-carcinogenesis
#14
Yannan Jiang, Xinming Qi, Xinyu Liu, Jun Zhang, Jun Ji, Zhenggang Zhu, Jin Ren, Yingyan Yu
Fbxw7, a subunit of the SCF E3 ubiquitin ligase, recognizes oncoprotein substrates and leads to their proteasomal degradation. Fbxw7 acts as a tumor suppressor via inducing apoptosis and growth arrest in various kinds of tumors. To clarify the initiating role in gastric carcinogenesis as well as the histologic characterization of tumor in Fbxw7 allele haploinsufficient mice, we generated Fbxw7 heterozygous knockout mice (Fbxw7+/-) and treated them with chemical carcinogen N-methyl-N-nitrosourea (MNU) at 5-6 weeks of age...
May 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28408485/styx-a-versatile-pseudophosphatase
#15
REVIEW
Veronika Reiterer, Krzysztof Pawłowski, Hesso Farhan
The pseudophosphatase STYX (serine/threonine/tyrosine interacting protein) is a catalytically inactive member of the protein tyrosine phosphatase family. We perform a phylogenetic analysis of STYX and ask how far does the pseudoenzyme status of STYX reaches in evolution. Based on our previous work, we use STYX as a showcase to discuss four basic modes of action that any given pseudoenzyme may exert. Our previous work on the effect of STYX on mitogen-activated protein kinase (MAPK) signaling led us to identify two complementary modes of action...
April 15, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28407575/fam83d-knockdown-regulates-proliferation-migration-and-invasion-of-colorectal-cancer-through-inhibiting-fbxw7-notch-1-signalling-pathway
#16
Yu Mu, Hongzhi Zou, Beibei Chen, Yixiao Fan, Suxia Luo
Colorectal cancer is one of the most common malignant tumors in the digestive system, and in China its incidence is rising in recent years. The FAM83D family with sequence similarity 83, member D is associated with the occurrence and development of various cancers. However, in human colorectal cancer, the biological function of FAM83D and its molecular mechanism are still little known. In our study, we found that FAM83D mRNA expression level was markedly up-regulated in colorectal cancerous tissues when compared with that of adjacent normal colon tissues...
June 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28404959/inhibition-of-the-prolyl-isomerase-pin1-enhances-the-ability-of-sorafenib-to-induce-cell-death-and-inhibit-tumor-growth-in-hepatocellular-carcinoma
#17
Min Zheng, Huijuan Xu, Xin-Hua Liao, Champ Peng Chen, Arina Li Zhang, Wenxian Lu, Long Wang, Dayun Yang, Jichuang Wang, Hekun Liu, Xiao Zhen Zhou, Kun Ping Lu
Hepatocellular carcinoma (HCC) is the sixth most common cancer, but is the second leading cause of cancer deaths, partially due to its heterogeneity and drug resistance. Sorafenib is the only medical treatment with a proven efficacy against advanced HCC, but its overall clinical efficacy is still modest. Therefore, a major challenge is how to improve its therapeutic efficacy. The unique prolyl isomerase Pin1 regulates numerous cancer-driving pathways. Notably, Pin1 is overexpressed in about 70% HBV-positive HCC patients and contributes to HCC tumorigenesis...
May 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28399885/next-generation-sequencing-and-fish-studies-reveal-the-appearance-of-gene-mutations-and-chromosomal-abnormalities-in-hematopoietic-progenitors-in-chronic-lymphocytic-leukemia
#18
Miguel Quijada-Álamo, María Hernández-Sánchez, Cristina Robledo, Jesús-María Hernández-Sánchez, Rocío Benito, Adrián Montaño, Ana E Rodríguez-Vicente, Dalia Quwaider, Ana-África Martín, María García-Álvarez, María Jesús Vidal-Manceñido, Gonzalo Ferrer-Garrido, María-Pilar Delgado-Beltrán, Josefina Galende, Juan-Nicolás Rodríguez, Guillermo Martín-Núñez, José-María Alonso, Alfonso García de Coca, José A Queizán, Magdalena Sierra, Carlos Aguilar, Alexander Kohlmann, José-Ángel Hernández, Marcos González, Jesús-María Hernández-Rivas
BACKGROUND: Chronic lymphocytic leukemia (CLL) is a highly genetically heterogeneous disease. Although CLL has been traditionally considered as a mature B cell leukemia, few independent studies have shown that the genetic alterations may appear in CD34+ hematopoietic progenitors. However, the presence of both chromosomal aberrations and gene mutations in CD34+ cells from the same patients has not been explored. METHODS: Amplicon-based deep next-generation sequencing (NGS) studies were carried out in magnetically activated-cell-sorting separated CD19+ mature B lymphocytes and CD34+ hematopoietic progenitors (n = 56) to study the mutational status of TP53, NOTCH1, SF3B1, FBXW7, MYD88, and XPO1 genes...
April 11, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28292439/integrated-molecular-characterization-of-uterine-carcinosarcoma
#19
Andrew D Cherniack, Hui Shen, Vonn Walter, Chip Stewart, Bradley A Murray, Reanne Bowlby, Xin Hu, Shiyun Ling, Robert A Soslow, Russell R Broaddus, Rosemary E Zuna, Gordon Robertson, Peter W Laird, Raju Kucherlapati, Gordon B Mills, John N Weinstein, Jiashan Zhang, Rehan Akbani, Douglas A Levine
We performed genomic, epigenomic, transcriptomic, and proteomic characterizations of uterine carcinosarcomas (UCSs). Cohort samples had extensive copy-number alterations and highly recurrent somatic mutations. Frequent mutations were found in TP53, PTEN, PIK3CA, PPP2R1A, FBXW7, and KRAS, similar to endometrioid and serous uterine carcinomas. Transcriptome sequencing identified a strong epithelial-to-mesenchymal transition (EMT) gene signature in a subset of cases that was attributable to epigenetic alterations at microRNA promoters...
March 13, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28287082/e3-ligase-fbxw7-is-critical-for-rig-i-stabilization-during-antiviral-responses
#20
Yinjing Song, Lihua Lai, Zhenlu Chong, Jia He, Yuanyuan Zhang, Yue Xue, Yiwei Xie, Songchang Chen, Ping Dong, Luoquan Chen, Zhimin Chen, Feng Dai, Xiaopeng Wan, Peng Xiao, Xuetao Cao, Yang Liu, Qingqing Wang
Viruses can escape from host recognition by degradation of RIG-I or interference with the RIG-I signalling to establish persistent infections. However, the mechanisms by which host cells stabilize RIG-I protein for avoiding its degradation are largely unknown. We report here that, upon virus infection, the E3 ubiquitin ligase FBXW7 translocates from the nucleus into the cytoplasm and stabilizes RIG-I. FBXW7 interacts with SHP2 and mediates the degradation and ubiquitination of SHP2, thus disrupting the SHP2/c-Cbl complex, which mediates RIG-I degradation...
March 13, 2017: Nature Communications
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