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https://www.readbyqxmd.com/read/28292439/integrated-molecular-characterization-of-uterine-carcinosarcoma
#1
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
#2
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
https://www.readbyqxmd.com/read/28280620/potential-actionable-targets-in-appendiceal-cancer-detected-by-immunohistochemistry-fluorescent-in-situ-hybridization-and-mutational-analysis
#3
Erkut Borazanci, Sherri Z Millis, Jeffery Kimbrough, Nancy Doll, Daniel Von Hoff, Ramesh K Ramanathan
BACKGROUND: Appendiceal cancers are rare and consist of carcinoid, mucocele, pseudomyxoma peritonei (PMP), goblet cell carcinoma, lymphoma, and adenocarcinoma histologies. Current treatment involves surgical resection or debulking, but no standard exists for adjuvant chemotherapy or treatment for metastatic disease. METHODS: Samples were identified from approximately 60,000 global tumors analyzed at a referral molecular profiling CLIA-certified laboratory. A total of 588 samples with appendix primary tumor sites were identified (male/female ratio of 2:3; mean age =55)...
February 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28280605/next-generation-sequencing-identifies-interactome-signatures-in-relapsed-and-refractory-metastatic-colorectal-cancer
#4
Benny Johnson, Laurence Cooke, Daruka Mahadevan
BACKGROUND: In the management of metastatic colorectal cancer (mCRC), KRAS, NRAS and BRAF mutational status individualizes therapeutic options and identify a cohort of patients (pts) with an aggressive clinical course. We hypothesized that relapsed and refractory mCRC pts develop unique mutational signatures that may guide therapy, predict for a response and highlight key signaling pathways important for clinical decision making. METHODS: Relapsed and refractory mCRC pts (N=32) were molecularly profiled utilizing commercially available next generation sequencing (NGS) platforms...
February 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28256213/update-on-molecular-findings-in-rhabdomyosarcoma
#5
REVIEW
Dina El Demellawy, Jean McGowan-Jordan, Joseph de Nanassy, Elizaveta Chernetsova, Ahmed Nasr
Rhabdomyosarcoma (RMS) is the most common malignant soft tissue tumour in children and adolescents. Histologically RMS resembles developing fetal striated skeletal muscle. RMS is stratified into different histological subtypes which appear to influence management plans and patient outcome. Importantly, molecular classification of RMS seems to more accurately capture the true biology and clinical course and prognosis of RMS to guide therapeutic decisions. The identification of PAX-FOXO1 fusion status in RMS is one of the most important updates in the risk stratification of RMS...
February 27, 2017: Pathology
https://www.readbyqxmd.com/read/28243320/construction-of-a-multiplex-mutation-hot-spot-pcr-panel-the-first-step-towards-colorectal-cancer-genotyping-on-the-gs-junior-platform
#6
Bálint Péterfia, Alexandra Kalmár, Árpád V Patai, István Csabai, András Bodor, Tamás Micsik, Barnabás Wichmann, Krisztina Egedi, Péter Hollósi, Ilona Kovalszky, Zsolt Tulassay, Béla Molnár
Background: To support cancer therapy, development of low cost library preparation techniques for targeted next generation sequencing (NGS) is needed. In this study we designed and tested a PCR-based library preparation panel with limited target area for sequencing the top 12 somatic mutation hot spots in colorectal cancer on the GS Junior instrument. Materials and Methods: A multiplex PCR panel was designed to amplify regions of mutation hot spots in 12 selected genes (APC, BRAF, CTNNB1, EGFR, FBXW7, KRAS, NRAS, MSH6, PIK3CA, SMAD2, SMAD4, TP53)...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28209614/distinct-interactions-of-ebp1-isoforms-with-fbxw7-elicits-different-functions-in-cancer
#7
Yuli Wang, Pengju Zhang, Yunshan Wang, Panpan Zhan, Chunyan Liu, Jian-Hua Mao, Guangwei Wei
The ErbB3 receptor binding protein EBP1 encodes two alternatively spliced isoforms p48 and p42. While there is evidence of differential roles for these isoforms in tumorigenesis, little is known about their underlying mechanisms. Here we demonstrate that EBP1 isoforms interact with the SCF-type ubiquitin ligase FBXW7 in distinct ways to exert opposing roles in tumorigenesis. EBP1 p48 bound to the WD domain of FBXW7 as an oncogenic substrate of FBXW7. EBP1 p48 binding sequestered FBXW7α to the cytosol, modulating its role in protein degradation and attenuating its tumor suppressor function...
February 16, 2017: Cancer Research
https://www.readbyqxmd.com/read/28199989/presence-of-cancer-associated-mutations-in-exhaled-breath-condensates-of-healthy-individuals-by-next-generation-sequencing
#8
Omar Youssef, Aija Knuuttila, Päivi Piirilä, Tom Böhling, Virinder Sarhadi, Sakari Knuutila
Exhaled breath condensate (EBC) is a non-invasive source that can be used for studying different genetic alterations occurring in lung tissue. However, the low yield of DNA available from EBC has hampered the more detailed mutation analysis by conventional methods. We applied the more sensitive amplicon-based next generation sequencing (NGS) to identify cancer related mutations in DNA isolated from EBC. In order to apply any method for the purpose of mutation screening in cancer patients, it is important to clarify the incidence of these mutations in healthy individuals...
February 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28196911/pseudophosphatase-as-e3-ubiquitin-ligase-inhibitor
#9
Nancy R Gough
The pseudophosphatase STYX prevents the substrate recognition subunit FBXW7 from binding the catalytic E3 ubiquitin ligase complex.
February 14, 2017: Science Signaling
https://www.readbyqxmd.com/read/28194040/abnormal-degradation-of-the-neuronal-stress-protective-transcription-factor-hsf1-in-huntington-s-disease
#10
Rocio Gomez-Pastor, Eileen T Burchfiel, Daniel W Neef, Alex M Jaeger, Elisa Cabiscol, Spencer U McKinstry, Argenia Doss, Alejandro Aballay, Donald C Lo, Sergey S Akimov, Christopher A Ross, Cagla Eroglu, Dennis J Thiele
Huntington's Disease (HD) is a neurodegenerative disease caused by poly-glutamine expansion in the Htt protein, resulting in Htt misfolding and cell death. Expression of the cellular protein folding and pro-survival machinery by heat shock transcription factor 1 (HSF1) ameliorates biochemical and neurobiological defects caused by protein misfolding. We report that HSF1 is degraded in cells and mice expressing mutant Htt, in medium spiny neurons derived from human HD iPSCs and in brain samples from patients with HD...
February 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/28149200/microrna-32-promotes-cell-proliferation-migration-and-suppresses-apoptosis-in-breast-cancer-cells-by-targeting-fbxw7
#11
Wei Xia, JueYu Zhou, HaiBo Luo, YunZhou Liu, CanCan Peng, WenLing Zheng, WenLi Ma
BACKGROUND: MicroRNAs are a class of small non-coding RNAs that are involved in many important physiological and pathological processes by regulating gene expression negatively. The purpose of this study was to investigate the effect of miR-32 on cell proliferation, migration and apoptosis and to determine the functional connection between miR-32 and FBXW7 in breast cancer. METHODS: In this study, quantitative RT-PCR was used to evaluate the expression levels of miR-32 in 27 breast cancer tissues, adjacent normal breast tissues and human breast cancer cell lines...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/28099906/genomic-characteristics-of-pancreatic-squamous-cell-carcinoma-an-investigation-by-using-high-throughput-sequencing-after-in-solution-hybrid-capture
#12
Meng-Dan Xu, Shu-Ling Liu, Yi-Zhong Feng, Qiang Liu, Meng Shen, Qiaoming Zhi, Zeyi Liu, Dong-Mei Gu, Jie Yu, Liu-Mei Shou, Fei-Ran Gong, Qi Zhu, Weiming Duan, Kai Chen, Junning Zhang, Meng-Yao Wu, Min Tao, Wei Li
Squamous cell carcinoma (SCC) of pancreas is a rare histotype of pancreatic ductal carcinoma which is distinct from pancreatic adenocarcinoma (AC). Although there are standard treatments for pancreatic AC, no precise therapies exist for pancreatic SCC. Here, we screened 1033 cases of pancreatic cancer and identified 2 cases of pure SCC, which were pathologically diagnosed on the basis of finding definite intercellular bridges and/or focal keratin peal formation in the tumor cells. Immunohistochemistry assay confirmed the positive expression of CK5/6 and p63 in pancreatic SCC...
January 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28078112/molecular-spectrum-of-kras-nras-braf-pik3ca-tp53-and-apc-somatic-gene-mutations-in-arab-patients-with-colorectal-cancer-determination-of-frequency-and-distribution-pattern
#13
Humaid O Al-Shamsi, Jeremy Jones, Yazan Fahmawi, Ibrahim Dahbour, Aziz Tabash, Reham Abdel-Wahab, Ahmed O S Abousamra, Kenna R Shaw, Lianchun Xiao, Manal M Hassan, Benjamin R Kipp, Scott Kopetz, Amr S Soliman, Robert R McWilliams, Robert A Wolff
BACKGROUND: The frequency rates of mutations such as KRAS, NRAS, BRAF, and PIK3CA in colorectal cancer (CRC) differ among populations. The aim of this study was to assess mutation frequencies in the Arab population and determine their correlations with certain clinicopathological features. METHODS: Arab patients from the Arab Gulf region and a population of age- and sex-matched Western patients with CRC whose tumors were evaluated with next-generation sequencing (NGS) were identified and retrospectively reviewed...
December 2016: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28069547/overexpression-of-mir-92a-promotes-the-tumor-growth-of-osteosarcoma-by-suppressing-f-box-and-wd-repeat-containing-protein-7
#14
Xuesheng Jiang, Xiongfeng Li, Fengfeng Wu, Hongliang Gao, Guorong Wang, Hua Zheng, Huajun Wang, Jianyou Li, Chao Chen
MicroRNAs (miRNAs) have been reported to be critical players in osteosarcoma (OS). Among numerous cancer-related miRNAs, the expression level of miR-92a and its potential role in OS has not been investigated. Here, We showed that overexpression of miR-92a was identified in OS specimens and cells compared to normal bone tissues. The high level of miR-92a was correlated with high T classification and advanced clinical stages of OS patients. Notably, miR-92a highly expressing OS patients showed a notably reduced survival rate...
March 30, 2017: Gene
https://www.readbyqxmd.com/read/28053206/gsk3b-mediated-phosphorylation-of-mcl1-regulates-axonal-autophagy-to-promote-wallerian-degeneration
#15
Shuji Wakatsuki, Shinji Tokunaga, Megumi Shibata, Toshiyuki Araki
Macroautophagy is a catabolic process, in which portions of cytoplasm or organelles are delivered to lysosomes for degradation. Emerging evidence has indicated a pathological connection between axonal degeneration and autophagy. However, the physiological function and induction mechanism of autophagy in axons remain elusive. We herein show that, through activation of BECLIN1, glycogen synthase kinase 3B (GSK3B)-mediated phosphorylation of BCL2 family member MCL1 induces axonal autophagy and axonal degeneration...
February 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28029553/somatic-mutation-detection-using-various-targeted-detection-assays-in-paired-samples-of-circulating-tumor-dna-primary-tumor-and-metastases-from-patients-undergoing-resection-of-colorectal-liver-metastases
#16
Nick Beije, Jean C Helmijr, Marjolein J A Weerts, Corine M Beaufort, Matthew Wiggin, Andre Marziali, Cornelis Verhoef, Stefan Sleijfer, Maurice P H M Jansen, John W M Martens
Assessing circulating tumor DNA (ctDNA) is a promising method to evaluate somatic mutations from solid tumors in a minimally-invasive way. In a group of twelve metastatic colorectal cancer (mCRC) patients undergoing liver metastasectomy, from each patient DNA from cell-free DNA (cfDNA), the primary tumor, metastatic liver tissue, normal tumor-adjacent colon or liver tissue, and whole blood were obtained. Investigated was the feasibility of a targeted NGS approach to identify somatic mutations in ctDNA. This targeted NGS approach was also compared with NGS preceded by mutant allele enrichment using synchronous coefficient of drag alteration technology embodied in the OnTarget assay, and for selected mutations with digital PCR (dPCR)...
October 10, 2016: Molecular Oncology
https://www.readbyqxmd.com/read/28008299/kras-mutation-as-a-potential-prognostic-biomarker-of-biliary-tract-cancers
#17
Masaaki Yokoyama, Hiroaki Ohnishi, Kouki Ohtsuka, Satsuki Matsushima, Yasuo Ohkura, Junji Furuse, Takashi Watanabe, Toshiyuki Mori, Masanori Sugiyama
BACKGROUND: The aim of this study was to identify the unique molecular characteristics of biliary tract cancer (BTC) for the development of novel molecular-targeted therapies. MATERIALS AND METHODS: We performed mutational analysis of KRAS, BRAF, PIK3CA, and FBXW7 and immunohistochemical analysis of EGFR and TP53 in 63 Japanese patients with BTC and retrospectively evaluated the association between the molecular characteristics and clinicopathological features of BTC...
2016: Japanese Clinical Medicine
https://www.readbyqxmd.com/read/28007894/the-pseudophosphatase-styx-targets-the-f-box-of-fbxw7-and-inhibits-scffbxw7-function
#18
Veronika Reiterer, Cristina Figueras-Puig, Francois Le Guerroue, Stefano Confalonieri, Manuela Vecchi, Dasaradha Jalapothu, Sandip M Kanse, Raymond J Deshaies, Pier Paolo Di Fiore, Christian Behrends, Hesso Farhan
The F-box protein FBXW7 is the substrate-recruiting subunit of an SCF ubiquitin ligase and a major tumor-suppressor protein that is altered in several human malignancies. Loss of function of FBXW7 results in the stabilization of numerous proteins that orchestrate cell proliferation and survival. Little is known about proteins that directly regulate the function of this protein. In the current work, we have mapped the interactome of the enigmatic pseudophosphatase STYX We reasoned that a catalytically inactive phosphatase might have adopted novel mechanisms of action...
February 1, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28000899/mir-367-promotes-the-proliferation-and-invasion-of-non-small-cell-lung-cancer-via-targeting-fbxw7
#19
Jing Xu, Weibing Wu, Jun Wang, Chenjun Huang, Wei Wen, Fei Zhao, Xinfeng Xu, Xianglong Pan, Wei Wang, Quan Zhu, Liang Chen
The involvement of miR-367 in lung cancer development remains unclear. In the present study, we analyzed the expression of miR-367 in tumor and adjacent tissue samples from 113 patients with non-small cell lung cancer (NSCLC) utilizing real-time PCR. miR-367 expression was significantly upregulated in the cancer tissues compared with non-cancer controls. Based on the median value of the miR-367 expression level, we divided the NSCLC patients into miR-367 high-expression and miR-367 low-expression groups. Overexpression of miR-367 was correlated with a poorer prognosis of NSCLC patients Chi-square (χ2) test showed a significant statistical correlation between tumor size, tumor stage, metastasis and miR-367 expression...
February 2017: Oncology Reports
https://www.readbyqxmd.com/read/28000896/mir%C3%A2-223%C3%A2-3p-regulates-cell-growth-and-apoptosis-via-fbxw7-suggesting-an-oncogenic-role-in-human-testicular-germ-cell-tumors
#20
Jikai Liu, Hao Shi, Xidan Li, Gang Chen, Catharina Larsson, Weng-Onn Lui
miR‑223‑3p is deregulated in several tumor types and plays an important role in tumorigenesis and progression. However, its role in the pathogenesis of testicular germ cell tumor (TGCT) remains uncharacterized. We previously demonstrated that miR‑223‑3p expression was increased in TGCTs compared with normal testes (NT), suggesting that miR‑223‑3p may have an oncogenic role in TGCT. Using published dataset and The Cancer Genome Atlas database, we validated higher miR‑223‑3p expression in TGCTs than NT, and found a negative correlation between miR-223-3p and FBXW7 mRNA expression levels...
February 2017: International Journal of Oncology
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