Chinnaiyan: WES of tumor/normal sample; try to comprehensive; include WGS (low-pass) and RNA-Seq. Fusions, CNV, indels, muts, expr. #AACR14
4:09pm April 7th 2014 via Hootsuite
Chinnaiyan: Upfront IRB, genet counseling; downstream a 'precision medicine tumor board', back to genetic counselor #AACR14
4:07pm April 7th 2014 via Hootsuite
Chinnaiyan: Challenges - which indiv to benefit, incidental findings, type of seq., turnaround time, interpretation, payment #AACR14
4:05pm April 7th 2014 via Hootsuite
Chinnaiyan: MI-ONCOSEQ program at Univ MI Program website: http://t.co/VZgyLBeLrm #AACR14
4:04pm April 7th 2014 via Hootsuite
First: Arul Chinnaiyan, Univ Mich "The application of integrative sequencing for precision medicine" #AACR14
4:03pm April 7th 2014 via Hootsuite
Symp: "Next-generation sequencing analysis as a tool to define the biologic basis of drug sensitivity". Chair, David Solit, MSKCC #AACR14
4:02pm April 7th 2014 via Hootsuite
RT @AppliedBio: #AACR14 Poster: Hotspot mutation & fus. transcript det. from same tumor sample http://t.co/IIjfxwGDYT http://t.co/PI8QNO
3:35pm April 7th 2014 via Hootsuite
RT @iontorrent: #AACR14 Poster: OncoNetwork collab study on dev. of Ion AmpliSeq RNA gene lung fusion panel. http://t.co/s3Htwoq8pM
3:31pm April 7th 2014 via Hootsuite
Bernstein: Hypoxia genes: some nutrient deprivation. Immune response: 1/5 samples had strong signal (histology - necrosis) #AACR14
3:22pm April 7th 2014 via Hootsuite
Bernstein: Unsupervised transcriptional model - examining cell cycle genes, of 5 samples >90% cells are not cycling #AACR14
3:21pm April 7th 2014 via Hootsuite
Bernstein: Showed a 2D plot illust. global inter- and intra-tumoral heterogeneity #AACR14
3:19pm April 7th 2014 via Hootsuite
Bernstein: Sees PDGFR anticorrelates with EGFR at the gene expression level in these single glioblastoma cells #AACR14
3:18pm April 7th 2014 via Hootsuite
Bernstein: Seeing single-cell variability in EGFR in these single primary glioblastoma cells #AACR14
3:17pm April 7th 2014 via Hootsuite
Bernstein: Primary CD45-depleted single GBM cells - use single-cell RNA-seq; detect ~6K genes, about 80 cells / sample #AACR14
3:15pm April 7th 2014 via Hootsuite
Bernstein: Core TF's expressed in CD133+ cells; have stem-like properties; can use to reprogram cells to de-differentiated state #AACR14
3:13pm April 7th 2014 via Hootsuite
Bernstein: Looked at genes downstream of the 4 core TF's, all are targets of each other; others ID'd as critical regulators #AACR14
3:11pm April 7th 2014 via Hootsuite
Bernstein: Added a fourth (OLIG2) and were able to propagate tumors in mice (in press) #AACR14
3:09pm April 7th 2014 via Hootsuite
Bernstein: Candidate TFs ID'd, cloned, overexpressed: but POU3F2+SOX2+SALL2 didn't induce tumorigen in mice #AACR14
3:08pm April 7th 2014 via Hootsuite
Bernstein: H3K27ac maps of cis regulatory elements per CSC vs. differentiated glioma state; 7.3K shared, 5.3K CSC, 3.7K DGC #AACR14
3:06pm April 7th 2014 via Hootsuite
Bernstein: Looking for a TF code for glioblastoma CSCs - candidate TFs inducing differentiation in culture #AACR14
3:04pm April 7th 2014 via Hootsuite
Bernstein: Thought there exist stem-like cells, refractory to therapy. Model in culture, CD133 2012 Nature http://t.co/Zhi1NW24a8 #AACR14
Bernstein: One goal: reconstruct and reprogram tumor propagating potential of cancer stem cells in glioblastoma. Mean surv. 15mo #AACR14
3:02pm April 7th 2014 via Hootsuite
Up Next: Brad Bernstein, Mass Gen Hospital. "Epigenetic regulation and hetergeneity in glioblastoma" #AACR14
3:00pm April 7th 2014 via Hootsuite
Melnick: Model shown for a non-canonical PRC1-like complex for poised transcriptional elongation #AACR14
2:56pm April 7th 2014 via Hootsuite
Melnick: EZH2 sets bivalent chromatin domains 2011 Nature review: http://t.co/slMHnXdreW #AACR14
2:49pm April 7th 2014 via Hootsuite
Melnick: Somatic mutations in EZH2 ref.: http://t.co/tFsU9OQyZA Knock-in mutants of EZH2/Y641F accelerates mouse B-cell lymphomas #AACR14
2:48pm April 7th 2014 via Hootsuite
Melnick: Work from 2001 referred to: http://t.co/NnHy4bvrH0 and afore-mentioned EZH2 required for germinal center formation #AACR14
2:42pm April 7th 2014 via Hootsuite
Melnick:These GC B-cells display features reminiscent of transformed cells - staving off infection but at a risk of lymphoma #AACR14
2:40pm April 7th 2014 via Hootsuite
Melnick: Upon B-cell activation, there's a massive growth phase, many point mutations in the B-cells that can become malignant #AACR14
2:37pm April 7th 2014 via Hootsuite
Next: Ari Melnick, Weill Cornell. "How deregulation of histone methyltransferase drive malignant transformation of B cells" #AACR14
2:33pm April 7th 2014 via Hootsuite
Brown: 250 samples, ~1/2 ER+: of those 134, 76 mets. Looked at Y537C - estrogen independent. ER muts inc. w/progression #AACR14
2:22pm April 7th 2014 via Hootsuite
Brown: Looking for ER mutations as drivers in br ca; no consistent patterns in papers since 1994 though TCGA #AACR14
2:20pm April 7th 2014 via Hootsuite
Brown: EZH2 is phosphorylated, and has methylation function, but may not be methylating chromatin, but other factors #AACR14
2:19pm April 7th 2014 via Hootsuite
Brown: EZH2 and shRNA knockdown, across normal, pr ca and castration-resistant; data suggests EZH2 and AR co-regulated #AACR14
2:14pm April 7th 2014 via Hootsuite
Brown: EZH2 in LNCaP-abl line, EZH2 up-regulated while H3K23me3 (product of prc2 complex) reduced. #AACR14
2:09pm April 7th 2014 via Hootsuite
Brown: Chinnaiyyan showed EZH2 one of the most highly over-exp genes in castration-resist. prostate ca #AACR14
2:08pm April 7th 2014 via Hootsuite
Brown: Prime movers are TF's. Polycomb repressive action of EZH2 illustrated in prostate ca #AACR14
Brown: Hormone-dep cancer questions about acquired resistance (clonal evol. or differentiation of cancer stem cell), other epi Q's #AACR14
2:06pm April 7th 2014 via Hootsuite
Next: Myles Brown, Dana-Farber Cancer Inst. "Genetic and epigenetic mechanisms of resistance to endocrine therapy" #AACR14
2:04pm April 7th 2014 via Hootsuite
Next: Myles Brown, Dana-Farber Cancer Inst. "Genetic and epigenetic mechanisms of resistance to endocrine therapy"
Stam.:Q:What if DHS were replaced with methylation, other states? A:With gene exp, can't get a lineage tree. A memory compartment #AACR14
2:01pm April 7th 2014 via Hootsuite
Stam.:Q:Involvement of superenhancers? A:The top group of DHSs, yes have TFs but further work needed. #AACR14
1:57pm April 7th 2014 via Hootsuite
Stam.:Q:(Bernstein) TF sites shared, is it way off? A:More than a 3D landscape, more like 100D. How far off? Depends on the tumor #AACR14
1:55pm April 7th 2014 via Hootsuite
Stam.: Ectopic regulatory landscape - dys-differentiation. Reactivation ES cell DHSs, loss/gain of TF's of oncogenes / suppressors #AACR14
1:54pm April 7th 2014 via Hootsuite
Stam.: 'Cancer is like Waddington's ball meet Tiger Woods' #AACR14
1:53pm April 7th 2014 via Hootsuite
Stam.: TFs: oncogenes key drivers of this regulatory transformation. FOXA1, ELF5, ER, GL12 etc. Suppressor TF's in turn are lost #AACR14
1:51pm April 7th 2014 via Hootsuite
Stam.: In br ca, T-cell leukemia, same basic pattern of ~80% reactivated from other cell-type development #AACR14
1:50pm April 7th 2014 via Hootsuite
Stam.: But in melanoma: "73% reactivated DHSs from other lineages', 24% from ES DHSs - disordered reactivation #AACR14
1:49pm April 7th 2014 via Hootsuite
Stam.: Regulatory landscape retrograde remodeling - from ES to melanocytes to melanoma: 257K to 171K to 163K DHSs #AACR14
1:48pm April 7th 2014 via Hootsuite
Stam.: Back to PCoA chart: cancer cells move toward the hESCs in the center of the plot. A 'retrograde remodeling' of landscape #AACR14
1:47pm April 7th 2014 via Hootsuite
