Jain: Microenv. shapes tumor biolology. 2009 Nature Medicine Vakoc et al PubMed: http://t.co/XvgpTP35GE #AACR14
6:49pm April 7th 2014 via Hootsuite
Jain: Each component of the microenv. is abnormal; if you can normalize / re-engineer it, you can improve outcomes. #AACR14
6:45pm April 7th 2014 via Hootsuite
8th Takamatusu Mem. Lecture: Rakesh Jain, Mass Gen Hosp.: Reengineering the tumor microenvironment to enhance cancer treatment #AACR14
6:34pm April 7th 2014 via Hootsuite
Carpten: Selected COLO 829 (CRL-1974) as it had data available on it already as a 'truth set' of 451 core mutations #AACR14
4:44pm April 7th 2014 via Hootsuite
Next: John Carpten, TGEN "Translation of cancer genomics knowledge to the clinic" #AACR14
4:32pm April 7th 2014 via Hootsuite
Chinnaiyan:Q:Handling heterogeneity? A:They see advanced cancers, heterogeneity isn't a large problem #AACR14
Chinnaiyan:Q:Include miRNA & epigenome? A:Needed to match available therapy. Can't link that data currently #AACR14
4:30pm April 7th 2014 via Hootsuite
Chinnaiyan: Distribution of categories: 57% Informative & actionable; 22 informative; 13 non-informative; 8% failed n=402 #AACR14
4:26pm April 7th 2014 via Hootsuite
Chinnaiyan: Reviewed 3 other vignettes - NAB2-STAT6 fusion; a rare FGFR kinas family fusion; and ESR1 mutations (all published) #AACR14
4:24pm April 7th 2014 via Hootsuite
Chinnaiyan: Found a KIF5B-RET fusion; highlighted this ref. Drilon et al Cancer Discov 2013 http://t.co/bf7NsyD4NF #AACR14
4:23pm April 7th 2014 via Hootsuite
Chinnaiyan:One example, adenocarcinoma, unk primary. Found 2 potentially sig CNV's, 3 germline variants; 41 somatic but no COSMIC #AACR14
4:20pm April 7th 2014 via Hootsuite
Chinnaiyan: Their precision med. tumor board - also genomics, clinical genetics, bioethics; try to classify into 5 groups #AACR14
4:12pm April 7th 2014 via Hootsuite
Chinnaiyan:Timeframe: Orig. 4w. Now ave is 6-8w 'not that acceptable'. Expect to get faster over time. #AACR14
4:10pm April 7th 2014 via Hootsuite
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
