scholarly journals Differentiating progressive from nonprogressive T1 bladder cancer by gene expression profiling: Applying RNA-sequencing analysis on archived specimens

2014 ◽  
Vol 32 (3) ◽  
pp. 327-336 ◽  
Author(s):  
Xuanhui Sharron Lin ◽  
Lan Hu ◽  
Kirley Sandy ◽  
Mick Correll ◽  
John Quackenbush ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bladder Cancer ◽  
Gene Expression Profiling ◽  
Rna Sequencing ◽  
Expression Profiling ◽  
Sequencing Analysis ◽  
Archived Specimens

Resolving driver events in MLL-r negative high-risk infant ALL.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 10030-10030
Author(s):  
Jennifer Seelisch ◽  
Matthew Zatzman ◽  
Federico Comitani ◽  
Fabio Fuligni ◽  
Ledia Brunga ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cell ◽  
High Risk ◽  
B Cell ◽  
Gene Expression Profiling ◽  
Rna Sequencing ◽  
Clinical Features ◽  
Expression Profiling ◽  
High Risk Infant ◽  
Childhood All

10030 Background: Infant acute lymphoblastic leukemia (ALL) is the only subtype of childhood ALL whose outcome has not improved over the past two decades. The most important prognosticator is the presence of rearrangements in the Mixed Lineage Leukemia gene (MLL-r), however, many patients present with high-risk clinical features but without MLL-r. We recently identified two cases of infant ALL with high-risk clinical features resembling MLL-r, but were negative for MLL-r by conventional diagnostics. RNA sequencing revealed a partial tandem duplication in MLL (MLL-PTD). We thus aimed to determine if MLL-PTD, other MLL abnormalities, or other genetic or transcriptomic features were driving this subset of high-risk infant ALL without MLL-r. Methods: We obtained 19 banked patient samples from the Children’s Oncology Group (COG) infant ALL trial (AALL0631) from MLL wildtype patients as determined by FISH and cytogenetics. Utilizing deep RNA-sequencing, we manually inspected the MLL gene for MLL-PTD, while also performing automated fusion detection and gene expression profiling in search of defining features of these tumors. Results: 3 additional MLL-PTDs were identified, all in patients with infant T-cell ALL, whereas both index cases were in patients with infant B-cell ALL. Gene expression profiling analysis revealed that all five MLL-PTD infants clustered together. Eight infants (7 with B-cell ALL) were found to have Ph-like expression. Five of these 8 infants were also found to have an IKZF1/JAK2 expression profile; one of these five had a PAX5-JAK2 fusion detected. Two infants (including the one noted above) had novel PAX5 fusions, known drivers of B-cell leukemia. Additional detected fusions included TCF3-PBX1 and TCF4-ZNF384. Conclusions: MLL-PTDs were found in both B- and T-cell infant ALL. Though Ph-like ALL has been described in adolescents and young adults, we found a substantial frequency of Ph-like expression among MLL-WT infants. Further characterization of these infants is ongoing. If replicated in other infant cohorts, these two findings may help explain the poor prognosis of MLL-WT ALL when compared to children with standard risk ALL, and offer the possibility of targeted therapy for select infants.

scholarly journals Gene expression profiling by targeted RNA sequencing in pathological stage I lung adenocarcinoma with a solid component

Lung Cancer ◽  
2020 ◽  
Vol 147 ◽  
pp. 56-63
Author(s):  
Yoshiteru Kidokoro ◽  
Tomohiko Sakabe ◽  
Tomohiro Haruki ◽  
Taichi Kadonaga ◽  
Kanae Nosaka ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lung Adenocarcinoma ◽  
Gene Expression Profiling ◽  
Rna Sequencing ◽  
Expression Profiling ◽  
Stage I ◽  
Solid Component ◽  
Pathological Stage

Association of myeloid suppressor cells with resistance to checkpoint blockade immunotherapy in urothelial carcinoma.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 559-559
Author(s):  
Debasish Sundi ◽  
Megan Christina Duggan ◽  
Himanshu Savardekar ◽  
Hyunwoo Kwon ◽  
Steven Sun ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bladder Cancer ◽  
Gene Expression Profiling ◽  
Immune Cells ◽  
Peripheral Blood ◽  
Expression Profiling ◽  
Suppressor Cells ◽  
Complete Response ◽  
Checkpoint Blockade ◽  
Myeloid Suppressor Cells

559 Background: Myeloid immune cells such as myeloid derived suppressor cells (MDSC) and tumor associated macrophages (TAM) have been hypothesized to cause resistance to immune checkpoint blockade (ICB). This is a pressing clinical problem for patients with bladder cancer. Here we determined if we could identify immune cells associated with resistance to ICB in the BBN963 mouse model, and if we could identify therapeutic strategies to target those same suppressor immune cells from patients with bladder cancer. Methods: BBN963 subcutaneous allografts were established in C57BL6/J mice. Response to anti-PD-L1 ICB was classified as partial or complete response according to RECIST criteria. Immune cell subsets with the tumors was evaluated by gene expression profiling and flow cytometry. Peripheral blood from patients with bladder cancer was collected under an IRB-approved protocol. MDSC were purified by flow sorting (CD11b+ CD33+ HLA-DRlow/neg) and screened for viability (Annexin-V staining) after 24 hours of exposure to a panel potential MDSC inhibitors. Results: 16/22 (72%) subjects met criteria for partial or complete response, while 6/22 (28%) were classified as anti-PD-L1 non-responders. Mice in the control group had a 0/10 (0%) response to isotype control (IgG) treatment. Monocytic MDSC (CD11b+ Ly6C+) were much more frequent among the intratumoral CD45+ cells of non-responding subjects as compared to control mice. Nanostring immune panel gene expression profiling revealed that combination treatment of tumor bearing mice with anti-PD-L1 plus ibrutinib (a putative MDSC inhibitor) decreased mRNA biomarkers of tumor-infiltrating macrophages. In vitro screening of patient-derived peripheral blood mononuclear cells showed that an inhibitor of the bromodomain and extraterminal domain (BET) family BRD4 specifically decreased MDSC viability. Conclusions: Monocytic MDSC appear to be associated with resistance to anti-PD-L1 ICB in a new murine model. Analysis of MDSC from patients with bladder cancer suggests that these myeloid suppressor cells can be specifically targeted.

scholarly journals Gene expression profiling reveals subgenome dominance during Brassica napus seed development

2020 ◽  
Author(s):  
Deirdre Khan ◽  
Dylan J. Ziegler ◽  
Jenna L. Kalichuk ◽  
Vanessa Hoi ◽  
Nina Hyunh ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Brassica Napus ◽  
Gene Expression Profiling ◽  
Rna Sequencing ◽  
Seed Development ◽  
Seed Coat ◽  
Expression Profiling ◽  
Early Stage ◽  
Transcriptional Networks

AbstractWe profiled the gene regulatory landscape of Brassica napus reproductive development using RNA sequencing. Comparative analysis of this nascent amphidiploid across the plant lifecycle revealed the contribution of each subgenome to plant reproduction. Global mRNA profiling revealed lower accumulation of Cn subgenome transcripts relative to the An subgenome. Subgenome-specific transcriptional networks identified distinct transcription factor families enriched in each of the An and Cn subgenome early in seed development. Global gene expression profiling of laser-microdissected seed subregions further reveal subgenome expression dynamics in the embryo, endosperm, and seed coat of early stage seeds. Transcription factors predicted to be regulators encoded by the An subgenome are expressed primarily in the seed coat whereas regulators encoded by the Cn subgenome were expressed primarily in the embryo. Data suggest subgenome bias are characteristic features of the B. napus seed throughout development, and that such bias might not be universal across the embryo, endosperm, and seed coat of the developing seed. Whole genome transcription factor networks identified BZIP11 as a transcriptional regulator of early B. napus seed development. Knockdown of BZIP11 using RNA interference resulted in a similar reduction in gene activity of predicted gene targets, and a reproductive-lethal phenotype. Taken together, transcriptional networks spanning both the An and Cn genomes of the B. napus seed can identify valuable targets for seed development research and that-omics level approaches to studying gene regulation in B. napus can benefit from both broad and high-resolution analyses.One Sentence SummaryGlobal RNA sequencing coupled with laser microdissection provides a critical resource to study subgenome bias in whole seeds and specific tissues of polyploid plants.

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