scholarly journals Mutation and genomic deletion status ofataxia telangiectasia mutated(ATM) andp53confer specific gene expression profiles in mantle cell lymphoma

2006 ◽  
Vol 103 (7) ◽  
pp. 2352-2357 ◽  
Author(s):  
Timothy C. Greiner ◽  
Chiranjib Dasgupta ◽  
Vincent V. Ho ◽  
Dennis D. Weisenburger ◽  
Lynette M. Smith ◽  
...  
Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5218-5218
Author(s):  
Diana Lucia Martínez Baquero ◽  
Ken H. Young ◽  
Roberto N. Miranda ◽  
L. Jeffrey Medeiros ◽  
Chi Young Ok

Background Mantle cell lymphoma (MCL) is an aggressive B cell neoplasm characterized the by t(11;14)(q13;q32)/CCND1-IGH resulting in overexpression of cyclin D1. Although indolent variants are recognized, MCL is generally aggressive and incurable. The MCL International Prognostic Index (MIPI), gene expression-based proliferation signatures, Ki-67 proliferation index, p53 expression, and aggressive histologic features are used for risk stratification, but the prognostic groups defined by each of these markers are clinically heterogeneous, demonstrating that each parameter alone does not fully account for the clinical behavior of these tumors. In this study, we investigated the gene expression profile of 60 cases of MCL and evaluated which genes had expression patterns that correlate with different clinical and histopathological parameters. Design A total of 60 excisional biopsy specimens of MCL were selected for gene expression profiling. Forty (66%) and 16 (26%) cases were untreated and relapse/persistent samples, respectively; in 4 this unknown was unknown. Biopsy sites included lymph nodes (n=38), spleen (n=10), tonsil (n=6) and various other extranodal tissue sites (n=6). The morphologic features were classic in 27 and aggressive (blastoid/pleomorphic) in 33 patients. MIPI was calculated in selected patients with nodal involvement and whose biopsy was an obtained prior to treatment. Each block contained tumor cells representing ≥ 80% of all cells in the biopsy specimen. RNA was extracted from formalin-fixed paraffin-embedded tissue using the Qiagen Allprep FFPE Kit after deparaffinization, according to the manufacturer's instructions. Gene expression was quantified in 200ng of RNA on the Nanostring™ platform. Normalization for RNA loading was performed using the geometric mean of 40 housekeeping genes with a cutoff value 20. Standard QC and data processing were performed using the nSolver™ Analysis Software. Adjusted p-values were used according to the Benjamini-Hochberg procedure. Results Gene expression profiling was different according to the site of involvement of MCL. Compared with nodal involvement, MCL involving spleen showed overexpression of VEGFA (p <0.01) and NOS (p <0.05). These genes are associated with angiogenesis via the PI3K signaling pathway. Similarly, tonsillar MCL showed overexpression of SFN and HSPB1 (p <0.01) compared with nodal MCL; these genes are related to the MAPK pathway. Different gene expression profiles were observed with respect to histology. Compared to classic variant, blastoid variant demonstrated overexpression of CDK4 (p <0.01) and underexpression of KAT2B and PIK3CG (p <0.01) in all cases. However, no significant differences were found in the gene expression profiles between the classic and pleomorphic variants. We also compared gene expression profiles based on the MIPI score. Compared to cases with a low MIPI score, those with a high MIPI score showed significant overexpression of several genes including SFN, COL11A2, HDAC6 and TP53 (p <0.01). Discussion MCL is a heterogeneous neoplasm, both clinically and genetically. In the present study, significant differences in gene expression profiles were observed based on site of involvement (spleen vs lymph node vs tonsil). However, we cannot exclude the possibility that the result reflects gene expression of non-lymphoma cells in the microenvironment since we did not extract RNA from lymphoma cells. We observed different gene expression profiles in the blastoid variant, but not in the pleomorphic variant compared to the classic variant, suggesting that the biology of pleomorphic variant is probably between the blastoid and the classic variants, possibly closer to the latter. Different gene expression profiles were found with respect to MIPI score, providing scientific support that the MIPI score, in addition to being a useful stratification factor in MCL patients, is reflecting differences in underlying biology of MCL. Disclosures No relevant conflicts of interest to declare.


Heart Rhythm ◽  
2013 ◽  
Vol 10 (3) ◽  
pp. 383-391 ◽  
Author(s):  
Yung-Hsin Yeh ◽  
Chi-Tai Kuo ◽  
Yun-Shien Lee ◽  
Yuan-Min Lin ◽  
Stanley Nattel ◽  
...  

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 51-51
Author(s):  
Patrick James McLaren ◽  
Anthony P Barnes ◽  
Willy Z Terrell ◽  
Gina M. Vaccaro ◽  
Jack Wiedrick ◽  
...  

51 Background: Predicting prognosis in esophageal cancer remains an unrealized goal despite studies linking constellations of genes to therapeutic response. In this study, we analyzed specific predictor genes expressed in tumor specimens from our institutional repository. Our aim was to determine if specific gene expression profiles are associated with pathologic complete response (pCR) after neoadjuvant chemo-radiotherapy (CRT). Methods: We investigated eleven genes identified from prior studies (CCL28, SPARC, S100A2, SPRR3, SIRT2, NOV, PERP, PAPSS2, DCK, DKK3, ALDH1) that have significant association with esophageal cancer progression. Patients with esophageal adenocarcinoma treated with neoadjuvant CRT followed by esophagectomy at our institution between January 2011 and July 2015 were included. Quantitative real-time polymerase chain reaction was conducted on pre-treatment biopsy specimens to determine gene expression. Patients were classified into two groups: 1) pCR and, 2) no or poor response (NR) after CRT based on final pathology report. An omnibus test using Mahalanobis distance was applied to evaluate overall genetic expression differences between groups. Log-rank tests compared the differential expression of individual genes. Results: 29 patients (11 pCR and 18 NR) were analyzed. Overall, gene expression profiles were significantly different between pCR and NR patients (p < 0.01). In particular, CCL28 was over-expressed in pCR (Log-HR: 1.53, 95%CI: 0.46-2.59, p = 0.005), and DKK3-was under-expressed in pCR patients (Log-HR: -1.03 95%CI: -1.97, -0.10, p = 0.031). Conclusions: Esophageal adenocarcinoma patients with a pCR after neoadjuvant therapy have genetic profiles that are significantly different from typical NR profiles. In our population, the genes CCL28 and DKK3 are potential predictors of treatment response.


BMC Cancer ◽  
2009 ◽  
Vol 9 (1) ◽  
Author(s):  
Cinzia Lavarino ◽  
Nai-Kong V Cheung ◽  
Idoia Garcia ◽  
Gema Domenech ◽  
Carmen de Torres ◽  
...  

Author(s):  
Karlijn J. Doorn ◽  
John J. P. Brevé ◽  
Benjamin Drukarch ◽  
Hendrikus W. Boddeke ◽  
Inge Huitinga ◽  
...  

2017 ◽  
Vol 37 (6) ◽  
Author(s):  
Marc Weidenbusch ◽  
Severin Rodler ◽  
Shangqing Song ◽  
Simone Romoli ◽  
Julian A. Marschner ◽  
...  

Notch and interleukin-22 (IL-22) signaling are known to regulate tissue homeostasis and respond to injury in humans and mice, and the induction of endogenous aryl hydrocarbon receptor (Ahr) ligands through Notch links the two pathways in a hierarchical fashion. However in adults, the species-, organ- and injury-specific gene expression of the Notch-AhR-IL22 axis components is unknown. We therefore performed gene expression profiling of DLL1, DLL3, DLL4, DLK1, DLK2, JAG1, JAG2, Notch1, Notch2, Notch3, Notch4, ADAM17/TNF-α ADAM metalloprotease converting enzyme (TACE), PSEN1, basigin (BSG)/CD147, RBP-J, HES1, HES5, HEY1, HEYL, AHR, ARNT, ARNT2, CYP1A1, CYP24A1, IL-22, IL22RA1, IL22RA2, IL10RB, and STAT3 under homeostatic conditions in ten mature murine and human organs. Additionally, the expression of these genes was assessed in murine models of acute sterile inflammation and progressive fibrosis. We show that there are organ-specific gene expression profiles of the Notch-AhR-IL22 axis in humans and mice. Although there is an overall interspecies congruency, specific differences between human and murine expression signatures do exist. In murine tissues with AHR/ARNT expression CYP1A1 and IL-22 were correlated with HES5 and HEYL expression, while in human tissues no such correlation was found. Notch and AhR signaling are involved in renal inflammation and fibrosis with specific gene expression changes in each model. Despite the presence of all Notch pathway molecules in the kidney and a model-specific induction of Notch ligands, IL-22 was only up-regulated in acute inflammation, but rapidly down-regulated during regeneration. This implies that for targeting injury responses, e.g. via IL-22, species-specific differences, injury type and time points have to be considered.


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