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Your search keyword '"Selaru, Florin M."' showing total 26 results
Start Over Author "Selaru, Florin M." Journal gastroenterology (00165085)
26 results on '"Selaru, Florin M."'

7. Whole-Exome Sequencing Analyses of Inflammatory Bowel Disease−Associated Colorectal Cancers.

Author

Robles, Ana I., Traverso, Giovanni, Zhang, Ming, Roberts, Nicholas J., Khan, Mohammed A., Joseph, Christine, Lauwers, Gregory Y., Selaru, Florin M., Popoli, Maria, Pittman, Meredith E., Ke, Xiquan, Hruban, Ralph H., Meltzer, Stephen J., Kinzler, Kenneth W., Vogelstein, Bert, Harris, Curtis C., and Papadopoulos, Nickolas

Abstract

Background & Aims A long duration of inflammatory bowel disease (IBD) increases the risk for colorectal cancer. Mutation analysis of limited numbers of genes has indicated that colorectal tumors that develop in patients with IBD differ from those of patients without IBD. We performed whole-exome sequencing analyses to characterize the genetic landscape of these tumors. Methods We collected colorectal tumor and non-neoplastic tissues from 31 patients with IBD and colorectal cancer (15 with ulcerative colitis, 14 with Crohn’s disease, and 2 with indeterminate colitis) and performed whole-exome sequencing analyses of the microdissected tumor and matched nontumor tissues. We identified somatic alterations by comparing matched specimens. The prevalence of mutations in sporadic colorectal tumors was obtained from previously published exome-sequencing studies. Results Two specimens had somatic mutations in the DNA proofreading or mismatch repair genes POLE , MLH1 , and MSH6 and the tumor cells had a hypermutable phenotype. The remaining tumors had, on average, 71 alterations per sample. TP53 was the most commonly mutated gene, with prevalence similar to that of sporadic colorectal tumors (63% of cases). However, tumors from the patients with IBD had a different mutation spectrum. APC and KRAS were mutated at significantly lower rates in tumors from patients with IBD than in sporadic colorectal tumors (13% and 20% of cases, respectively). Several genes were mutated more frequently or uniquely in tumors from patients with IBD, including SOX9 and EP300 (which encode proteins in the WNT pathway), NRG1 (which encodes an ERBB ligand), and IL16 (which encodes a cytokine). Our study also revealed recurrent mutations in components of the Rho and Rac GTPase network, indicating a role for noncanonical WNT signaling in development of colorectal tumors in patients with IBD. Conclusions Colorectal tumors that develop in patients with IBD have distinct genetic features from sporadic colorectal tumors. These findings could be used to develop disease-specific markers for diagnosis and treatment of patients with IBD and colorectal cancer. [ABSTRACT FROM AUTHOR]

Published
2016
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13. The miR-106b-25 Polycistron, Activated by Genomic Amplification, Functions as an Oncogene by Suppressing p21 and Bim.

Author

Kan, Takatsugu, Sato, Fumiaki, Ito, Tetsuo, Matsumura, Nobutoshi, David, Stefan, Cheng, Yulan, Agarwal, Rachana, Paun, Bogdan C., Jin, Zhe, Olaru, Alexandru V., Selaru, Florin M., Hamilton, James P., Yang, Jian, Abraham, John M., Mori, Yuriko, and Meltzer, Stephen J.

Subjects
GENE amplification, ONCOGENES, BARRETT'S esophagus, CANCER invasiveness, TISSUE analysis, ESOPHAGEAL cancer, REVERSE transcriptase polymerase chain reaction, NON-coding RNA
Abstract

Background & Aims: Barrett''s esophagus (BE) is a highly premalignant disease that predisposes to the development of esophageal adenocarcinoma (EAC); however, the involvement of microRNAs (miRs) in BE-EAC carcinogenic progression is not known. Methods: Esophageal cultured cells (HEEpiC, QhTRT, ChTRT, GihTRT, and OE-33) and esophageal tissues (22 normal epithelia, 24 BE, and 22 EAC) were studied. MiR microarrays and quantitative reverse-transcription polymerase chain reaction (RT-PCR) were employed to explore and verify differentially expressed miRs. Quantitative genomic PCR was performed to study copy number variation at the miR-106b-25 polycistron and MCM7 gene locus on chromosome 7q22.1. In vitro cell proliferation, cell cycle, and apoptosis assays and in vivo tumorigenesis experiments were performed to elucidate biologic effects of the miR-106b-25 polycistron. Western blotting and luciferase assays were performed to confirm direct messenger RNA (mRNA) targeting by the miR-106b-25 polycistron. Results: The miR-106b-25 polycistron exerted potential proliferative, antiapoptotic, cell cycle-promoting effects in vitro and tumorigenic activity in vivo. MiRs-93 and -106b targeted and inhibited p21, whereas miR-25 targeted and inhibited Bim. This polycistron was up-regulated progressively at successive stages of neoplasia, in association with genomic amplification and overexpression of MCM7. In addition, miRs-93 and -106b decreased p21 mRNA, whereas miR-25 did not alter Bim mRNA, suggesting the following discrete miR effector mechanisms: (1) for p21, mRNA degradation; (2) for Bim, translational inhibition. Conclusions: The miR-106b-25 polycistron is activated by genomic amplification and is potentially involved in esophageal neoplastic progression and proliferation via suppression of 2 target genes: p21 and Bim. [Copyright &y& Elsevier]

Published
2009
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20. 197 A Multicenter, Double-Blinded Validation Study of Methylation Biomarkers for Progression Prediction in Barrett's Esophagus.

Author

Jin, Zhe, Cheng, Yulan, Gu, Jessie, Zheng, Yingye, Mori, Yuriko, Olaru, Alexandru, Paun, Bogdan C., Kan, Takatsugu, Hamilton, James P., Selaru, Florin M., David, Stefan, Wolfsen, Herbert C., Wallace, Michael B., Shaheen, Nicholas J., Washington, Mary Kay, Wang, Jean S., Canto, Marcia I., Bhattacharyya, Achyut K., Nelson, Mark A., and Wagner, Paul D.

Published
2009
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