scholarly journals Dual regulatory role of CCNA2 in modulating CDK6 and MET‐mediated cell‐cycle pathway and EMT progression is blocked by miR‐381‐3p in bladder cancer

2018 ◽  
Vol 33 (1) ◽  
pp. 1374-1388 ◽  
Author(s):  
Jiangfeng Li ◽  
Yufan Ying ◽  
Haiyun Xie ◽  
Ke Jin ◽  
Huaqing Yan ◽  
...  
2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 680-680
Author(s):  
Ramya Thota ◽  
Mark Andrew Lewis ◽  
Lincoln Nadauld ◽  
Derrick S. Haslem ◽  
Terence Duane Rhodes ◽  
...  

680 Background: Cyclin Dependent Kinases (CDKs) play a significant role in cell cycle regulation. Aberrations involving the cell cycle pathway genes can lead to uncontrolled cell proliferation and genomic instability. These could potentially be targeted with CDK4/6 inhibitors. The frequency and type of these alterations in GI tumors is largely unknown. Methods: We analyzed the frequency of abnormalities in cell cycle genes in patients with diverse GI malignancies (colorectal, liver, pancreas, gastroesophageal, anal, appendix) that underwent next generation sequencing from January 2013 to August 2017. Results: Aberrations in the cell cycle pathway were identified in 33 of 299 (11%) of cancers. The frequency of aberrations was as follows: CDKN2A/B in 10 (30.3%), CCND1 in 7 patients (pts) (21.2%), CCND2 in 2 pts (6%), CEBPA in 2 pts (6%), CDK6 in 2 pts (6%), CDK8 in 2 pts (6%) and CDK2 in 1 (3%). Alteration involving multiple genes of cell cycle noted in 7 patients (21.2%) with combination of CCND1 and CDKN2A being most common combination. The cell cycle checkpoint defects were most frequently seen in 9 pts with colon (27%), 8 pts with hepatobiliary (27%), 8 pts with pancreatic (24%), 7 pts with esophageal (21%), and less commonly in small bowel (6%) and GIST (6%). Conclusions: The alterations in the cell cycle pathway are most common in certain GI tumors mainly colon, pancreatic, hepatobiliary and esophageal tumors. Future clinical trials exploring the potential role of targeted agents such as CDK4/6 inhibitors alone or in combination with other targeted agents such as MEK inhibitors requires further exploration in these tumors.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e16006-e16006
Author(s):  
Arash Samiei ◽  
Pritam Tayshetye ◽  
Angela Sanguino ◽  
Ralph Miller ◽  
John Lyne ◽  
...  

e16006 Background: Platinum-resistant muscle-invasive bladder cancer (prMIBC) is the main cause of bladder cancer mortality. Recent advances in next-generation DNA sequencing (NGS) has allowed characterization of the molecular landscape of MIBC. Yet, the correlation between the molecular alteration and the poor outcome of prMIBC is still lacking. This study aims to explore the potential genetic alterations in this group of patients. Methods: A retrospective study of prMIBC patients that had NGS molecular profiling at a single center from November 2014 to October 2018 was conducted. The prMIBC was defined as patients who had a significant residual disease or disease progression following cisplatin-based chemotherapy in a neoadjuvant or metastatic disease setting. NGS was performed on formalin-fixed paraffin-embedded tissue samples through commercial companies. Results: A total of 17 prMIBC with the median age of 65 [51-74] years old were included in this study. At the end of the study, 8 patients were alive and 9 deceased. A total of 58 mutations were identified. 7 of the 58 genes were mutated in ≥20% of cases: TP53 (65%), TERT promoter -124C > T (59%), ARID1A (35%), CDKN2A/B (30%), RB1 (24%), PIK3CA (24%), and FLCN (20%). Less frequent mutations (12% each) include MDM2, AKT2, KDM6A, SMARCA4, FGF3, FGF4, BRCA2, STAG2, and CCNE1 genes. Analysis of the mutations revealed key pathways including TP53/cell cycle pathway altered in 82%, PI-3K/mTOR pathway in 71%, Telomere regulation in 59%, SWI/SNF complex in 35% and histone modification in 24% of cases. Conclusions: Among patients with prMIBC, mutations in the p53/cell cycle pathway are the most common findings. Genetic alteration involving the PI-3K/mTOR pathway is frequently associated with prMIBC, which could provide an important lead for a predictive model and targeted intervention. Interestingly, the TERT promoter -124C > T mutation is a very common molecular alteration in prMIBC that has not been reported before. Telomere regulation may play a role in contributing to platinum-resistance in bladder cancer. Further elucidation of the molecular landscape in prMIBC on a larger scale would help to establish a molecular model to predict platinum-response in MIBC.


2020 ◽  
Author(s):  
Zhaowei Zhu ◽  
Fujiang Chang ◽  
Junxiao Liu ◽  
Jiange Wang ◽  
Xuepei Zhang

2013 ◽  
Vol 539 (1) ◽  
pp. 92-98 ◽  
Author(s):  
Maki Kitagawa ◽  
Naomi Niisato ◽  
Atsushi Shiozaki ◽  
Mariko Ohta-Fujimoto ◽  
Shigekuni Hosogi ◽  
...  

2005 ◽  
Vol 274 (1-2) ◽  
pp. 47-52 ◽  
Author(s):  
Miwako Kato Homma ◽  
Yoshimi Homma
Keyword(s):  

2006 ◽  
Vol 175 (4S) ◽  
pp. 317-317
Author(s):  
Xifeng Wu ◽  
Jian Gu ◽  
H. Barton Grossman ◽  
Christopher I. Amos ◽  
Carol Etzel ◽  
...  

2005 ◽  
Vol 173 (4S) ◽  
pp. 214-215 ◽  
Author(s):  
Daniel Cho ◽  
Xiao Fang Ha ◽  
J. Andre Melendez ◽  
Louis J. Giorgi ◽  
Badar M. Mian

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