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https://www.readbyqxmd.com/read/28732357/profiling-cancer-related-gene-mutations-in-oral-squamous-cell-carcinoma-from-japanese-patients-by-targeted-amplicon-sequencing
#1
Takafumi Nakagaki, Miyuki Tamura, Kenta Kobashi, Ryota Koyama, Hisayo Fukushima, Tomoko Ohashi, Masashi Idogawa, Kazuhiro Ogi, Hiroyoshi Hiratsuka, Takashi Tokino, Yasushi Sasaki
Somatic mutation analysis is a standard practice in the study of human cancers to identify mutations that cause therapeutic sensitization and resistance. We performed comprehensive genomic analyses that used PCR target enrichment and next-generation sequencing on Ion Proton semiconductor sequencers. Forty-seven oral squamous cell carcinoma (OSCC) samples and their corresponding noncancerous tissues were used for multiplex PCR amplification to obtain targeted coverage of the entire coding regions of 409 cancer-related genes (covered regions: 95...
July 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28732331/an-evaluation-of-dna-damage-in-human-lymphocytes-and-sperm-exposed-to-methyl-methanesulfonate-involving-the-regulation-pathways-associated-with-apoptosis
#2
Khaled Habas, Mojgan Najafzadeh, Adolf Baumgartner, Martin H Brinkworth, Diana Anderson
Exposure to DNA-damaging agents produces a range of stress-related responses. These change the expression of genes leading to mutations that cause cell cycle arrest, induction of apoptosis and cancer. We have examined the contribution of haploid and diploid DNA damage and genes involved in the regulation of the apoptotic process associated with exposure, The Comet assay was used to detect DNA damage and quantitative RT-PCR analysis (qPCR) to detect gene expression changes in lymphocytes and sperm in response to methyl methanesulfonate...
June 23, 2017: Chemosphere
https://www.readbyqxmd.com/read/28731047/targeted-next-generation-sequencing-supports-epidermoid-metaplasia-of-the-esophagus-as-a-precursor-to-esophageal-squamous-neoplasia
#3
Aatur D Singhi, Christina A Arnold, Dora M Lam-Himlin, Marina N Nikiforova, Lysandra Voltaggio, Marcia I Canto, Kevin M McGrath, Elizabeth A Montgomery
Esophageal epidermoid metaplasia is a rare condition that involves the proximal-to-middle third of the esophagus. It is sharply demarcated and defined histologically by epithelial hyperplasia, a prominent granular cell layer, and superficial hyperorthokeratosis. In addition, preliminary studies have suggested an association between esophageal epidermoid metaplasia and esophageal squamous neoplasia (squamous dysplasia and esophageal squamous cell carcinoma). To further characterize esophageal epidermoid metaplasia and better define its relationship to squamous neoplasia of the esophagus, we performed targeted next-generation sequencing on uninvolved esophageal squamous mucosa and matching esophageal epidermoid metaplasia specimens from 18 patients...
July 21, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28730642/myc-expression-and-translocation-analyses-in-low-grade-and-transformed-follicular-lymphoma
#4
S M Aukema, R van Pel, I Nagel, S Bens, R Siebert, S Rosati, E van den Berg, A G Bosga-Bouwer, R E Kibbelaar, M Hoogendoorn, G W van Imhoff, J C Kluin-Nelemans, P M Kluin, M Nijland
Low grade follicular lymphoma (FL1/2) has an annual risk of transformation of approximately 3% which is associated with aberrations in CDKN2A/B, TP53 and MYC. Like in DLBCL high MYC expression in transformed FL (tFL) might predict a MYC breakpoint. We quantified MYC expression by immunohistochemistry and digital analysis in 41 paired biopsies from 20 patients with FL1/2 with subsequent transformation and in 4 isolated biopsies of tFL. As controls 28 biopsies of FL1/2 without transformation (median follow up 105 months) and 9 FL3A/B were analyzed...
July 21, 2017: Histopathology
https://www.readbyqxmd.com/read/28730258/morphology-with-immunohistochemical-and-genetic-profiling-of-high-grade-neuroendocrine-carcinoma-of-colon-a-case-report-with-review-of-literature
#5
Andrzej Wincewicz, Artur Kowalik, Sebastian Zięba, Stanisław Sułkowski, Stanisław Góźdź
Here we present a challenging case of a hepatic flexure colon tumor of 61-year-old woman with no primary lesion of lung cancer. Immunohistochemistry was applied and 50 genes were analyzed by next-generation sequencing (NGS) technology. The tumor contained medium to large size neoplastic cells with evident nucleoli to be diagnosed poorly differentiated neuroendocrine predominantly large cell carcinoma of colon [G3: World Health Organization (WHO) 2010] (pT3 N0: 7th edition pTNM). Cytokeratin (CK) AE1÷AE3 staining was predominantly membranous with partial distribution in "dot-like" pattern in perinecrotic cancer fields to be reminiscent of small cell carcinoma...
2017: Romanian Journal of Morphology and Embryology, Revue Roumaine de Morphologie et Embryologie
https://www.readbyqxmd.com/read/28729302/vosaroxin-in-combination-with-decitabine-in-newly-diagnosed-older-patients-with-acute-myeloid-leukemia-or-high-risk-mds
#6
Naval Daver, Hagop Kantarjian, Guillermo Garcia-Manero, Elias Jabbour, Gautam Borthakur, Mark Brandt, Sherry Pierce, Kenneth Vaughan, Jing Ning, Graciela M Nogueras González, Keyur Patel, Jeff Jorgensen, Naveen Pemmaraju, Tapan Kadia, Marina Konopleva, Michael Andreeff, Courtney DiNardo, Jorge Cortes, Renee Ward, Adam Craig, Farhad Ravandi
Vosaroxin is an anti-cancer quinolone derived DNA topoisomerase II inhibitor. We investigated vosaroxin with decitabine in patients ≥ 60 years of age with newly diagnosed acute myeloid leukemia (AML) (n=58) or myelodysplastic syndrome (MDS) (≥ 10% blasts) (n=7) in a phase 2 non-randomized trial. The initial 22 patients received vosaroxin 90 mg/m2 on Days 1 and 4 with decitabine 20 mg/m2 Days 1-5 every 4-6 weeks for up to 7 cycles. Due to high incidence of mucositis the subsequent 43 patients received vosaroxin 70 mg/m2 Days 1 and 4...
July 20, 2017: Haematologica
https://www.readbyqxmd.com/read/28729121/multiple-myeloma-genomics-a-systematic-review
#7
REVIEW
Casey J Weaver, Joseph D Tariman
OBJECTIVES: This integrative review describes the genomic variants that have been found to be associated with poor prognosis in patients diagnosed with multiple myeloma (MM). Second, it identifies MM genetic and genomic changes using next-generation sequencing, specifically whole-genome sequencing or exome sequencing. DATA SOURCE: A search for peer-reviewed articles through PubMed, EBSCOhost, and DePaul WorldCat Libraries Worldwide yielded 33 articles that were included in the final analysis...
July 18, 2017: Seminars in Oncology Nursing
https://www.readbyqxmd.com/read/28729047/p53-deregulation-in-epstein-barr-virus-associated-gastric-cancer
#8
Joana Ribeiro, Mariana Malta, Ana Galaghar, Fernanda Silva, Luís Pedro Afonso, Rui Medeiros, Hugo Sousa
TP53 is a tumour suppressor gene frequently mutated in human cancers; nevertheless, in EBV-associated malignancies mutations are uncommon despite frequent deregulation of the p53 pathway. In this study, we aimed to investigate p53 expression, TP53 mRNA levels and TP53 mutations in EBV-associated gastric carcinoma (EBVaGC). A case-control study was performed using 46 patients: 15 EBVaGC and 31 EBV-negative GC (EBVnGC) cases. p53 expression was detected by immunohistochemistry (IHC), the evaluation of p53 mRNA levels was performed by RT-qPCR and TP53 mutations were investigated only in EBVaGC cases using the DNA sanger sequencing method...
July 17, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28726739/5-aza-2-2-difluroro-deoxycytidine-nuc013-a-novel-nucleoside-dna-methyl-transferase-inhibitor-and-ribonucleotide-reductase-inhibitor-for-the-treatment-of-cancer
#9
Richard Daifuku, Zhenbo Hu, Yogen Saunthararajah
Tumor suppressor genes can be silenced genetically as well as epigenetically. One approach to reversing epigenetic suppression of tumor suppressor genes is to inhibit DNA methyl transferase. 5-aza-2',2'-diflurorodeoxycytidine (NUC013) is a novel DNA methyl transferase and ribonucleotide reductase inhibitor that is a more potent inhibitor of growth than decitabine in the NCI 60 cancer cell line panel. NUC013 is more active than decitabine against p53-null/mutant cancer cell lines (p = 0.027) but is even more so against p53 wild-type (WT) cell lines (p = 0...
July 20, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28725540/the-pathology-and-molecular-genetics-of-sarcomatoid-renal-cell-carcinoma-a-mini-review
#10
REVIEW
Shuanzeng Wei, Tahseen Al-Saleem
Sarcomatoid renal cell carcinoma is a highly aggressive tumor. It is not a distinct histologic entity as it can be found in any subtypes of renal cell carcinoma. Recent molecular and genetic evidence suggest that sarcomatoid component is transformed from a common progenitor of the associated renal cell carcinoma, and the TP53 gene plays a pivotal role in this process. The presence of sarcomatoid carcinoma indicates poor prognosis, which also correlates with the amount of the sarcomatoid component. Therefore, the presence and quantity of sarcomatoid component should be reflected in pathology reports...
2017: Journal of Kidney Cancer and VHL
https://www.readbyqxmd.com/read/28723644/fir-haplodeficiency-promotes-splicing-to-pyruvate-kinase-m2-in-mice-thymic-lymphoma-tissues-revealed-by-six-plex-tandem-mass-tag-quantitative-proteomic-analysis
#11
Asako Kimura, Kouichi Kitamura, Guzhanuer Ailiken, Mamoru Satoh, Toshinari Minamoto, Nobuko Tanaka, Fumio Nomura, Kazuyuki Matsushita
The switch of pyruvate kinase (PK) M1 to PKM2 is pivotal for glucose metabolism in cancers. The PKM1/M2 shift is controlled by the alternative splicing of two mutually exclusive exons in the PKM gene. PKM1 is expressed in differentiated tissues, whereas PKM2 is expressed in cancer tissues. This study revealed that the haplodeficiency of FUSE-binding protein (FBP)-interacting repressor (FIR), a transcriptional repressor of the c-myc gene, contributed to the splicing of PKM1 to PKM2 in mice thymic lymphoma and/or T-cell type acute lymphoblastic leukemia (T-ALL) using six-plex tandem mass tag (TMT) quantitative proteomic analysis...
July 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28722212/active-human-papillomavirus-involvement-in-barrett-s-dysplasia-and-oesophageal-adenocarcinoma-is-characterized-by-wild-type-p53-and-aberrations-of-the-retinoblastoma-protein-pathway
#12
Shanmugarajah Rajendra, Tao Yang, Wei Xuan, Prateek Sharma, Darren Pavey, Cheong Soon Lee, Son Le, Josephine Collins, Bin Wang
We have previously demonstrated that transcriptionally active high-risk HPV (hr-HPV) is strongly incriminated in Barrett's dysplasia (BD) and oesophageal adenocarcinoma (OAC) using mainly fresh frozen tissue. This study aimed to identify biomarkers of active HPV infection in Barrett's metaplasia, (BM)/BD/OAC by immunohistochemical staining (IHC) of formalin-fixed paraffin embedded (FFPE) tissue for aberrations of p53 and the retinoblastoma (pRb) pathway which are targets for the viral oncoproteins, E6/E7 respectively...
July 19, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28722124/pancreatic-undifferentiated-carcinoma-with-osteoclast-like-giant-cells-is-genetically-similar-to-but-clinically-distinct-from-conventional-ductal-adenocarcinoma
#13
Claudio Luchini, Antonio Pea, Gemma Lionheart, Andrea Mafficini, Alessia Nottegar, Nicola Veronese, Peter Chianchiano, Lodewijk A A Brosens, Michaël Noë, G Johan A Offerhaus, Raluca Yonescu, Yi Ning, Giuseppe Malleo, Giulio Riva, Paola Piccoli, Ivana Cataldo, Paola Capelli, Giuseppe Zamboni, Aldo Scarpa, Laura D Wood
Undifferentiated carcinoma of the pancreas with osteoclast-like giant cells (UCOGC) is currently considered a morphologically and clinically distinct variant of pancreatic ductal adenocarcinoma (PDAC). In this study, we report clinical and pathological features of a series of 22 UCOGC, including the whole exome sequencing of 8 UCOGC. We observed that 60% of the UCOGC contained a well-defined epithelial component and that patients with pure UCOGC had a significantly better prognosis than did those with an UCOGC with an associated epithelial neoplasm...
July 19, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28722109/genomic-signatures-of-adenosquamous-carcinoma-of-the-pancreas-pasc
#14
Yuan Fang, Zhe Su, Jing Xie, Ruidong Xue, Qi Ma, Yanmeng Li, Yifan Zhao, Zeshi Song, Xiongxiong Lu, Hongwei Li, Chenghong Peng, Bai Fan, Baiyong Shen
In pancreatic cancer (PC), adenosquamous carcinoma of the pancreas (PASC) containing both ductal adenocarcinoma and squamous carcinoma in the same tumor represents ~ 4% of the total incidence. To date, the genomic features of this mixed tumor are still unknown. We analyzed genomes of 17 PASCs and 34 ductal adenocarcinomas (PDACs), showing that PASC carried highly enriched TP53 mutations and 3p loss compared to PDAC. Furthermore, we uncovered that adenomatous and squamous components of PASC harbored comparable genomic alterations, suggesting that two cellular components are developed from the same progenitor cancer cells...
July 19, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28721068/patients-harboring-alk-rearrangement-adenocarcinoma-after-acquired-resistance-to-crizotinib-and-transformation-to-small-cell-lung-cancer-a-case-report
#15
You-Cai Zhu, Xing-Hui Liao, Wen-Xian Wang, Chun-Wei Xu, Wu Zhuang, Li-Hua Zhong, Kai-Qi Du, Yan-Ping Chen, Gang Chen, Mei-Yu Fang
Anaplastic lymphoma kinase (ALK) rearrangement responds to ALK tyrosine kinase inhibitors (TKIs) in lung cancer. Many cases ultimately acquire resistance to crizotinib. Resistance, including ALK-dominant or ALK non-dominant, mechanisms have been described. Transformation to small-cell lung cancer is rare. Herein, we report a 49-year-old man diagnosed with adenocarcinoma, who was negative for EGFR and ALK genes as detected by reverse transcription polymerase chain reaction, and was treated with crizotinib. A new biopsy showed a small-cell lung cancer after disease progression...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28718916/the-genetic-landscape-of-endometrial-clear-cell-carcinomas
#16
Deborah F DeLair, Kathleen A Burke, Pier Selenica, Raymond S Lim, Sasinya N Scott, Sumit Middha, Abhinita S Mohanty, Donavan T Cheng, Michael F Berger, Robert A Soslow, Britta Weigelt
Clear cell carcinoma of the endometrium is a rare type of endometrial cancer generally associated with an aggressive clinical behavior. Here we sought to define the repertoire of somatic genetic alterations in endometrial clear cell carcinomas (ECCs) and whether ECCs could be classified into the molecular subtypes described for endometrial endometrioid and serous carcinomas. We performed a rigorous histopathological review, immunohistochemical analysis and massively parallel sequencing targeting 300 cancer-related genes of 32 pure ECCs...
July 18, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28718760/cd25-expression-and-outcomes-in-older-patients-with-acute-myelogenous-leukemia-treated-with-plerixafor-and-decitabine
#17
John N Allan, Gail J Roboz, Gulce Askin, Ellen Ritchie, Joseph Scandura, Paul Christos, Duane C Hassane, Monica L Guzman
We investigated CD25 expression in older (≥60 years) patients with new acute myelogenous leukemia treated with decitabine and plerixafor. Patients resistant to therapy or survival ≤1 year had significantly higher percentages of CD25(pos) myeloid blasts in baseline bone marrow. CD25(pos) patients had an increased odds of resistance compared to CD25(neg) patients (p = .015). In univariate analysis, we found CD25(pos) patients had inferior survival compared to CD25(neg) (p = .002). In patients with intermediate risk cytogenetics, CD25(pos) status stratified patients associating with inferior survival (p = ...
July 18, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28718729/the-novel-autophagy-inhibitor-elaiophylin-exerts-antitumor-activity-against-multiple-myeloma-with-mutant-tp53-in-part-through-endoplasmic-reticulum-stress-induced-apoptosis
#18
Wang Gaoxiang, Zhou Pan, Chen Xing, Lei Zhao, Tan Jiaqi, Yang Yang, Yong Fang, Jianfeng Zhou
Elaiophylin is a natural compound and a novel and potent inhibitor of late stage autophagy with outstanding antitumor activity in human ovarian cancer cells. However, the possible biological effects and functional linkage between elaiophylin and multiple myeloma (MM) have not been explored. This study aimed to assess the effect of elaiophylin on MM cells with mutant TP53 and the possible molecular mechanism. The results suggested that elaiophylin exerted anti-myeloma activity by inducing apoptosis and proliferation arrest...
July 18, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28716577/apoptosis-related-genes-induced-in-response-to-ketamine-during-early-life-stages-of-zebrafish
#19
Luís M Félix, Cindy Serafim, Ana M Valentim, Luís M Antunes, Manuela Matos, Ana M Coimbra
Increasing evidence supports that ketamine, a widely used anaesthetic, potentiates apoptosis during development through the mitochondrial pathway of apoptosis. Defects in the apoptotic machinery can cause or contribute to the developmental abnormalities previously described in ketamine-exposed zebrafish. The involvement of the apoptotic machinery in ketamine-induced teratogenicity was addressed by assessing the apoptotic signals at 8 and 24 hpf following 20min exposure to ketamine at three stages of early zebrafish embryo development (256 cell, 50% epiboly and 1-4 somites stages)...
July 14, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28714959/o-glcnacylation-modulates-bmi-1-protein-stability-and-potential-oncogenic-function-in-prostate-cancer
#20
Y Li, L Wang, J Liu, P Zhang, M An, C Han, Y Li, X Guan, K Zhang
The Polycomb group transcriptional repressor Bmi-1 often overexpressed and participated in stem cells self-renewal and tumorigenesis initiating of prostate cancer. In this progression, Bmi-1 protein was regulated by transcription and post-translational modifications (PTMs). Nobly, the underlying PTMs regulation of Bmi-1 is poorly known. Here we use co-immunoprecipitation show that in C4-2 cell line, Bmi-1 directly interacted with OGT which is the only known enzyme catalyzed the O-GlcNAcylation in human. Furthermore, we identified that Ser255 is the site for Bmi-1 O-GlcNAcylation, and O-GlcNAcylation promoted Bmi-1 protein stability and its oncogenic activity...
July 17, 2017: Oncogene
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