Hicks: For aggressive prostate ca? Can get normal adj. along with tumor; Looking at 5 regions by Gleason 9, clear differences #AACR14
1:52pm April 8th 2014 via Hootsuite
Hicks: Looking at bulk DNA baseline and post-treatment bulk / post-trtmt single cells have chr20 amplifications #AACR14
1:47pm April 8th 2014 via Hootsuite
Hicks: Example stories on breast ca: observe CCND1 CNV from one cell; another cell has androgen receptor (?!?); another CCNE1... #AACR14
1:46pm April 8th 2014 via Hootsuite
Hicks: Shown data from 2011 Navin et al Nature paper http://t.co/5psWYTgo3N to follow tumor dev over time; CNVs as a marker #AACR14
1:39pm April 8th 2014 via Hootsuite
Hicks: Using nuclei, using low-coverage CNV, good comparison to million's of cells; can detect 10x and 11x integer CN's clearly #AACR14
1:38pm April 8th 2014 via Hootsuite
Hicks: One way is to use FLDM's C1 Autoprep; do sparse NGS for CNV, or targeted for SNV #AACR14
1:36pm April 8th 2014 via Hootsuite
Hicks:Single-cell techniques labeled 'Method of the Year' in 2013. Nature Methods ref: http://t.co/g4VVAOmQee #AACR14
Next: James Hicks, CSHL "Single-cell genomic and clonal anlaysis of breast and prostate" #AACR14
1:34pm April 8th 2014 via Hootsuite
.@MsStephKayB You are welcome! Shame that there weren't more in attendance - it is the 3rd day at 7am - I certainly did enjoy it! #AACR14
12:40pm April 8th 2014 via Hootsuite in reply to
Janne: Showing combinations in EGFR TKI naive pts was not very effective for lung adenocarcinoma #AACR14
11:49am April 8th 2014 via Hootsuite
Janne: Lung adenocarcinoma pie chart of known genotypes - went from ~75% unk in '03 to ~45% unk in 2014 #AACR14
11:46am April 8th 2014 via Hootsuite
Next: Pasi Janne, Dana Farber Cancer Inst. "Combination therapies for lung cancer: Opportunities and challenges" #AACR14
11:44am April 8th 2014 via Hootsuite
Nowak: Mapped cell growth in a 3D model over time, with effect of treatment as a video movie #AACR14
11:43am April 8th 2014 via Hootsuite
.@kennamshaw Great to meet you too! @illumina kicked me out of their soiree, although my many friends there wouldn't let me leave!
11:41am April 8th 2014 via Hootsuite in reply to
Nowak:: "Sequential therapy is a recipe for failure"; advocates simultaneous therapy #AACR14
11:40am April 8th 2014 via Hootsuite
Nowak: Each mut: 10^-9 with each cell div; modeled melanoma trtmnt in this 2013 Bozic et al eLife paper http://t.co/xvotRpd35J #AACR14
11:39am April 8th 2014 via Hootsuite
Nowak: Math of comb. treatment: n1 = pt mut's conferring resistance to drug1; n2 - pt mut's for drug2; n12 combination of mut's #AACR14
11:35am April 8th 2014 via Hootsuite
Nowak: Prob. of no resistant cells at start of trtmnt: 10^-33. 1/1M cancer cells (~3k) were resistant at start of trtmt. #AACR14
11:34am April 8th 2014 via Hootsuite
Nowak: With Vogelstein in 2010 Diaz et al in Nature http://t.co/dK4SmdIEe1 Emergence of mutant KRAS - did it evolve during trmt? #AACR14
11:32am April 8th 2014 via Hootsuite
Nowak: Looking at CML in response kinetics from Michor et al Nature 2005 paper: http://t.co/Fk3jJHPG5l From stem cells, turnover rt #AACR14
11:30am April 8th 2014 via Hootsuite
Nowak:...to the establishment of the parental clone. Overall 20y from initiation to the death of the indivdual #AACR14
11:28am April 8th 2014 via Hootsuite
Nowak: That paper mapped spatially the passenger mutations; but the time was on the order of 12 years from initiation... #AACR14
Nowak:Shared equations of passengers, drivers tested in 2010 Yachida et al Nature http://t.co/MufTJaiK4q in pancreatic cancer #AACR14
11:27am April 8th 2014 via Hootsuite
Nowak:Passenger mut's accumulate in a linear, molecular-clock fashion. Proportional to cell division time #AACR14
11:25am April 8th 2014 via Hootsuite
Nowak:Refers to this 2010 Bozic PNAS paper http://t.co/DvRx7MguZx about accumulation of driver mutations over time-frame years #AACR14
11:24am April 8th 2014 via Hootsuite
Nowak: The two its is a certain rate; but CIN inactivation occurs very quickly. Only one or a few CIN genes needed for 2 TSP genes #AACR14
11:23am April 8th 2014 via Hootsuite
Nowak: A mathematical model: hitting both alleles; and/or CIN mut's (chromosomal instab.) - could cause fast LOH #AACR14
11:21am April 8th 2014 via Hootsuite
Nowak:CAll colon ca's have genomic instability; when does it arise? Before activation of first tumor suppressor mut? #AACR14
11:20am April 8th 2014 via Hootsuite
Nowak: (A mathematical biologist estimates the no. of sheep v. well, just isn't that great at distinguishing between dog and sheep) #AACR14
11:19am April 8th 2014 via Hootsuite
Trent: (Commentary - what a great talk. Makes getting up early worthwhile.) #AACR14
10:51am April 8th 2014 via Hootsuite
Trent: Only 2/485% (0.4%) of other ov ca cases lose SMARCA4 via IHC; 13/15 (87%) have it in SCCOHT ones #AACR14
10:50am April 8th 2014 via Hootsuite
Trent: Cp to other ovarian carcinomas, ID'd SMARCA4 in 9/12 cases, truncating mut's. Germline mut's preceeded the ov ca #AACR14
10:48am April 8th 2014 via Hootsuite
Trent: Example 2 - recent Nature Gen Ramos et al paper: http://t.co/XPyY4adK1B A rare, highly malignant ovarian cancer #AACR14
10:46am April 8th 2014 via Hootsuite
Trent: Looking at rare mucosal melanoma trials in canines that would be impossible to perform in humans #AACR14
10:44am April 8th 2014 via Hootsuite
Trent: Points to PLoS One 2014 Paoloni et al paper here: http://t.co/Cvh9YqY7LH Now looking at novel trial designs in canine #AACR14
Trent: No 'UV signature' in canine melanoma, looks like it is driven by CNV's. 2/3 are BRAFwt, RASwt #AACR14
10:42am April 8th 2014 via Hootsuite
Trent: Points to this 2014 Simson et al paper: http://t.co/IGAAkrbZB2 about how useful a canine model is for melanoma #AACR14
10:41am April 8th 2014 via Hootsuite
Trent: On to the 'bark' part: canine model is relevant to human cancer, also for drug development #AACR14
10:40am April 8th 2014 via Hootsuite
Trent: Is also using some proteomic data in collaboration with Petticoin and LeBoer at Goerge Mason Univ #AACR14
10:37am April 8th 2014 via Hootsuite
Trent: Idea is to capture collective prior knowledge, use N=1 data, put back into context, develop 'drug rule network' #AACR14
10:33am April 8th 2014 via Hootsuite
Trent: Made 9 synthetic fusion constructs as part of their validation process, sensitivity to detect spike-ins #AACR14
10:32am April 8th 2014 via Hootsuite
Trent: 2D plot of coverage vs. tumor fraction, and power to detect variant (in color); part of validation process #AACR14
10:31am April 8th 2014 via Hootsuite
Trent: 4d analysis for prod, 1d for res. side. Sens., spec., host of validation metrics. WGS, WES, WGS insert, RNA, CNV arrays #AACR14
10:30am April 8th 2014 via Hootsuite
Trent: (GEMM is ass'd with SU2C). About a 2w turnaround; deep exome, long-insert WGS, germline, analysis. HiSeq 2.5K, Dell donation #AACR14
10:29am April 8th 2014 via Hootsuite
Trent: Reviewed the pilot trial requirements, FDA and CMS rec's had long list of criteria. 2.4k pages of doc's, IRB approved #AACR14
10:21am April 8th 2014 via Hootsuite
Trent: GEMM requires non-BRAF V600 mut. melanoma, also failed or ineligible for immunotherapy; a 'double-curse' #AACR14
10:20am April 8th 2014 via Hootsuite
Trent: Focus on difficult to treat - credits Sosman (Vanderbilt), Sekulic (Mayo); 'Genomics Enabled Medicine for Melanoma' GEMM #AACR14
10:18am April 8th 2014 via Hootsuite
Trent: non-BRAF V600E melanoma trtmt. - testing the concept of a collection of Rx's with treatment options, genomically informed #AACR14
10:17am April 8th 2014 via Hootsuite
Trent: Lentiviral infection of melanoma BRAF/L567V for PLX-sensitivity: showed a secondary BRAF conferring PLX resistance #AACR14
10:16am April 8th 2014 via Hootsuite
Trent: Looked at mother's primary, lung met, brain met, shoulder relapse, 2 fetal met's. Took flow-sorted FFPE and did aCGH, WES #AACR14
10:13am April 8th 2014 via Hootsuite
