Prediction of response to bortezomib and dexamethasone resistance in myeloma (MM) by novel mutations in the NFKB pathway

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8007-8007
Author(s):  
W. J. Chng ◽  
J. J. Keats ◽  
M. Chesi ◽  
A. Baker ◽  
L. K. Bruhn ◽  
...  
Keyword(s):  
Gene Expression ◽  
Fluorescent In Situ Hybridization ◽  
Randomized Study ◽  
Proteasome Inhibitors ◽  
Oligonucleotide Array ◽  
Comparative Genomic ◽  
Large Gene ◽  
Dexamethasone Resistance ◽  
Nfkb Pathway

8007 Background: We recently described mutations in multiple genes in MM patients that lead to the activation of the non- canonical NF-KB pathway. Among the mutated genes, TRAF3 is the most commonly affected, and is inactivated in about 20% of patients. In this study, we further defined the clinical significance of TRAF3 inactivation in MM. Methods: Deletion of TRAF3 was identified by array- based comparative genomic hybridization using Agilent Human Genome CGH 44k oligonucleotide array and confirmed by fluorescent in situ hybridization. Mutations were detected by sequencing. We use a TRAF3 gene expression cut-off (derived from 127 Mayo clinic patients) as a surrogate for TRAF3 inactivation to investigate its association with Translocations and Cyclin D genetic subtypes, response rates, and survival using 2 large gene expression dataset: UAMS dataset (559 newly diagnosed patients treated with Total therapy II and III) and Millenium datasets (213 relapsed patients entered into randomized study of bortezomib versus dexamethasone). Results: A normalized expression level of less than 0.6 identified all but three of the known TRAF3 inactivated cases in the Mayo dataset (p<0.0001). Using this cut-off, TRAF3 inactivated cases were enriched for t(4;14) (26%, p=0.00002) and rarely D1 (mostly hyperdiploid) (9%, p=9.6E-10) in all 3 datasets. TRAF3 inactivation did not affect survival of patients treated with transplant-based therapy (UAMS and Mayo dataset) but was strongly associated with bortezomib response (89% TRAF3 low versus 40% TRAF3 normal, p0.6 had similar PFS with the two treatment. Conclusion: Mutations resulting in TRAF3 inactivation are common, particularly in non-hyperdiploid MM, and predict for response to bortezomib and resistance to dexamethasone suggesting that inhibition of the non-canonical NF-KB pathway may be one of the principle mechanisms of action of proteasome inhibitors in MM. No significant financial relationships to disclose.

scholarly journals Detection of luxS gene expression under stressing factors for biofilm formation by Propionibacterium acidipropionici and Propionibacterium freudenreichii

2015 ◽  
Vol 5 (2) ◽  
pp. 604-613 ◽  
Author(s):  
Danitza Xiomara Romero ◽  
Oscar Víctor Cárdenas Alegría ◽  
Víctor Hugo Cavero Olguin ◽  
María Teresa Álvarez Aliaga
Keyword(s):  
Gene Expression ◽  
Biofilm Formation ◽  
Fluorescent In Situ Hybridization ◽  
Culture Conditions ◽  
Propionibacterium Freudenreichii ◽  
Pathogenic Microorganisms ◽  
Luxs Gene ◽  
Propionibacterium Acidipropionici ◽  
Biofilm Reactors

Gene expression constitutes an important role in cellular communication, setting mechanisms for biofilm formation. Genes can be used as molecular markers to monitor viability, stability and maintenance of biofilm eg. in biofilm reactors, bioremediation and biotransformation frequently under stressing conditions to enhance or limit the biofilm formation. In the present study, no pathogenic microorganisms of industrial interest were used. Propionibacterium freudenreichiisubsp. shermanii DSM 4902T and P. acidipropionici DSM 4900Tstrains cannot produce biofilm in culture conditions previously reported. In this regard, chemical culture conditions were modified to stimulate biofilm formation in both strains and determine that under stressing conditions such as 0.6 M NaCl, 1.8 M glucose and 10 gL-1 yeast extract both Propionibacterium produce biofilm. Finally, luxS expression was identified in biofilm of both strains by modified fluorescent in situ hybridization expression (FISH expression).

scholarly journals Neuronal migration genes and a familial translocation t(3;17): which genes are implicated in the phenotype?

2019 ◽  
Author(s):  
Meriam HADJ AMOR ◽  
Sarra Dimassi ◽  
Hanen Hannachi ◽  
Amel Taj ◽  
Adnene Mlika ◽  
...  
Keyword(s):  
Neuronal Migration ◽  
Critical Region ◽  
Fluorescent In Situ Hybridization ◽  
Array Comparative Genomic Hybridization ◽  
Gene Dosage ◽  
Comparative Genomic ◽  
History Of ◽  
Cytogenetic Characterization

Abstract Background: While Miller-Dieker syndrome critical region deletions are well known delineated anomalies, submicroscopic duplications in this region have recently emerged as a new distinctive syndrome. So far, only few cases have been described overlapping 17p13.3 duplications. Methods: In this study, we report on clinical and cytogenetic characterization of two new cases involving 17p13.3 and 3p26 chromosomal regions in two sisters with familial history of lissencephaly. Fluorescent In Situ Hybridization and array Comparative Genomic Hybridization were performed. Results: A deletion including the critical region of the Miller-Dieker syndrome of at least 2,9 Mb and a duplication of at least 3,6 Mb on the short arm of chromosome 3 were highlighted in one case. The opposite rearrangements, duplication 17p13.3 and deletion 3p were seen in the second case. This double chromosome aberration is the result of an adjacent 1:1 meiotic segregation of a maternal reciprocal translocation t(3;17)(p26.2;p13.3). Conclusions: 17p13.3 and 3p26 deletions have a clear range of phenotypic features while duplications still have uncertain clinical significance. However, we could suggest that regardless of the type of the rearrangement, the gene dosage and interactions of CNTN4, CNTN6 and CHL1 in the 3p26 and PAFAH1B1, YWHAE in 17p13.3 could result in different clinical spectrums.

scholarly journals Visualization of spatial gene expression in plants by modified RNAscope fluorescent in situ hybridization

Plant Methods ◽  
2020 ◽  
Vol 16 (1) ◽  
Author(s):  
Shyam Solanki ◽  
Gazala Ameen ◽  
Jin Zhao ◽  
Jordan Flaten ◽  
Pawel Borowicz ◽  
...  
Keyword(s):  
Gene Expression ◽  
In Situ Hybridization ◽  
Fluorescent In Situ Hybridization

scholarly journals Neuronal migration genes and a familial translocation t(3;17): Candidate genes implicated in the phenotype

2019 ◽  
Author(s):  
Meriam HADJ AMOR ◽  
Sarra Dimassi ◽  
Hanen Hannachi ◽  
Amel Taj ◽  
Adnene Mlika ◽  
...  
Keyword(s):  
Neuronal Migration ◽  
Critical Region ◽  
Fluorescent In Situ Hybridization ◽  
Array Comparative Genomic Hybridization ◽  
Gene Dosage ◽  
Comparative Genomic ◽  
History Of ◽  
Cytogenetic Characterization

Abstract Background: While Miller-Dieker syndrome critical region deletions are well known delineated anomalies, submicroscopic duplications in this region have recently emerged as a new distinctive syndrome. So far, only few cases have been described overlapping 17p13.3 duplications. Methods: In this study, we report on clinical and cytogenetic characterization of two new cases involving 17p13.3 and 3p26 chromosomal regions in two sisters with familial history of lissencephaly. Fluorescent In Situ Hybridization and array Comparative Genomic Hybridization were performed. Results: A deletion including the critical region of the Miller-Dieker syndrome of at least 2,9 Mb and a duplication of at least 3,6 Mb on the short arm of chromosome 3 were highlighted in one case. The opposite rearrangements, 17p13.3 duplication and 3p deletion were observed in the second case. This double chromosomal aberration is the result of an adjacent 1:1 meiotic segregation of a maternal reciprocal translocation t(3;17)(p26.2;p13.3). Conclusions: 17p13.3 and 3p26 deletions have a clear range of phenotypic features while duplications still have an uncertain clinical significance. However, we could suggest that regardless of the type of the rearrangement, the gene dosage and interactions of CNTN4, CNTN6 and CHL1 in the 3p26 and PAFAH1B1, YWHAE in 17p13.3 could result in different clinical spectrums.

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