Wetterskog: Overview of castration-resistant prostate cancer, with Rx treatment course. Looked at abiraterone resist in plasma #NGDx16
8:45am August 25th 2016 via Hootsuite
Wetterskog: Androgens binds AR to translocate to nucleus, stim proliferatoin, activates expression of PSA #NGDx16
8:41am August 25th 2016 via Hootsuite
Daniel Wetterskog (Inst CR UK) Clinical applications of tracking plasma AR aberrations in castration-resistant prostate cancer #NGDx16
8:40am August 25th 2016 via Hootsuite
Moshkevich: Natera's work (and method) reported here '15 ref https://t.co/M31FwCfp2v #NGDx16
8:38am August 25th 2016 via Hootsuite
Moshkevich: Impt take-home is using massively multiplex PCR with allele haplotype information to detect CNV to 1% #NGDx16
8:36am August 25th 2016 via Hootsuite
Solomon Moshkevich (VP Products Natera): Novel methods for detecting CNV at tumor fractions <1% #NGDx16
8:35am August 25th 2016 via Hootsuite
Thierry: Mentions a new company, DiaDx for commercializing technology #NGDx16
6:18pm August 24th 2016 via Hootsuite
Thierry: Showed emergence of resistant KRAS clones in ctDNA after different number of treatment cycles https://t.co/RI7a9uTd4V #NGDx16
Thierry: Showed unpublished data showing mutational status of baseline / post-Rx #NGDx16
6:15pm August 24th 2016 via Hootsuite
Thierry: '14 ASB qPCR-based IntPlex method ref https://t.co/AMLjBOOHnx #NGDx16
Thierry: FPs by delay between tissue and plasma collection; their IntPlex assay was first to detect more in ccfDNA cp to tissue #NGDx16
6:12pm August 24th 2016 via Hootsuite
Thierry: BRAF V600E, 7% in tissue, 14% in ccfDNA. Looked at all factors (v busy chart) bet tissue and plasma #NGDx16
6:11pm August 24th 2016 via Hootsuite
Thierry: Clinical utility in Kplex2, 11 ctrs; 43% KRAS exon2 mut by tissue; 57% by ccfDNA #NGDx16
6:10pm August 24th 2016 via Hootsuite
Thierry: 'Storage up to 8y shown'. First guideline in Streck: can use within 5d post-collection 'without any difference' #NGDx16
6:07pm August 24th 2016 via Hootsuite
Thierry: After extraction -20C, only 3 F/T cycles. Long-term: up to 9mos at -20C or -80C. "No difference" 2mL plasma or ccfDNA #NGDx16
6:06pm August 24th 2016 via Hootsuite
Thierry: -20C plasma storage or -80C if 'extraction is delayed'. Up to 2 F/T cycles. 4C to 3h if extraction not delayed #NGDx16
6:04pm August 24th 2016 via Hootsuite
Thierry: At 1% sens, '30% of mutants would have been missed'. TAm-Seq at 0.2%. '13 ref https://t.co/3v1F5sVQzW 4-6h post-coll #NGDx16
6:03pm August 24th 2016 via Hootsuite
Thierry: 21% were very low (<<1%) in distribution shown. Shows chart cp TAm-Seq (Inivata); BEAMing, single locus dPCR, IntPlex. #NGDx1
6:01pm August 24th 2016 via Hootsuite
Thierry: Shows data how widely the mutational load will vary. Median 4.79%; 75% <25%; 5% <0.01%; range 0.004% to 98% #NGDx16
5:59pm August 24th 2016 via Hootsuite
Thierry: Descr. Intplex, an ASB qPCR-based metod. Can detect 1:260K WT, quant for ccfDNA, mut ccfDNA. Sens 'is the major point' #NGDx16
5:58pm August 24th 2016 via Hootsuite
RT @h2so4hurts: NH: Based on a metagenomic shot-gun - need to get away from 16s because you miss stuff #NGDx16
5:56pm August 24th 2016 via Hootsuite
Thierry: ctDNA comes from both malignant and non-malignant cells; non-tumor cfDNA also exists. #NGDx16
5:55pm August 24th 2016 via Hootsuite
Thierry: Need for strong guidelines for preanalytic; ccfDNA is not in common to CTC; 50x - 1000x GE's cp to CTCs #NGDx16
5:54pm August 24th 2016 via Hootsuite
Thierry:Shows list of circ DNA for oncology, '10 - '16 w/5 trials ongoing, 3 finished. All but one prospective, blind, multi-ctr #NGDx16
5:53pm August 24th 2016 via Hootsuite
Alain Thierry (INSERM) Eval of circ DNA analysis in oncology: multi-center clinical trials in Europe; std collection of material #NGDx16
5:51pm August 24th 2016 via Hootsuite
Q: Static genotype; a place for fn analysis in blood? Velculescu: Other ways (exosomes), may be helpful (CUP) #NGDx16
5:50pm August 24th 2016 via Hootsuite
Q: How to increase specificity for early detection? Velculescu: Digital PCR, problem of subclones; mutations sneak into blood cells #NGDx16
5:49pm August 24th 2016 via Hootsuite
Q: is <0.2% a tech or biological limit? Velculescu: GE may not be much more helpful than that #NGDx16
5:47pm August 24th 2016 via Hootsuite
Velculescu: Shows fig from '14 rev https://t.co/hR3xhgM6yL Plenty of opportunities: dynamic genomes; actionability; early det #NGDx16
5:45pm August 24th 2016 via Hootsuite
Velculescu: "A high fraction would find in plasma alone at StgII, making a gigantic difference in CRC' #NGDx16
5:43pm August 24th 2016 via Hootsuite
Velculescu: Showing unpublished matched tumor/plasma, CRC by StgI through StgIV. #NGDx16
5:42pm August 24th 2016 via Hootsuite
Velculescu: One approach is WGS of CRC; showed data that only used 1/4th of a HiSeq lane. Pushing lower AF down to 0.2% #NGDx16
5:41pm August 24th 2016 via Hootsuite
Velculescu: For early detection is the 'holy grail, hampered by challenges of technology and understanding of biology' #NGDx16
5:39pm August 24th 2016 via Hootsuite
Velculescu: Resistance to anti-EGFR blockade in CRC '15 Nature https://t.co/EAvIrfO38J suggesting new avenues of Rx #NGDx16
5:38pm August 24th 2016 via Hootsuite
Velculescu: But in panc ca: determining what is actionable, 1/3d of these pts had potentially actionable muts #NGDx16
5:36pm August 24th 2016 via Hootsuite
Velculescu: Level of ctDNA and time of detection over std imaging: 3mos vs 9mos, giving add'l 6mos where you can do something #NGDx16
5:35pm August 24th 2016 via Hootsuite
Velculescu:Detection of residual disease '15 ref https://t.co/pLFGZgoSKq K-M of chr regulator for panc ca; a 'logical approach' #NGDx16
Velculescu: In CRC plasma, direct detection of ERBB2 and CDK6 amplification. Developed 60-gene PGDx panel, both sequence and rearr's #NGDx16
5:32pm August 24th 2016 via Hootsuite
Velculescu: Rearrangements via Leary '12 https://t.co/cxkT7cjIry and Bettegowda '14 https://t.co/Whc4Fe3gkt #NGDx16
5:30pm August 24th 2016 via Hootsuite
Velculescu: Actionability - >75% have tumor-specific mutations. Overviews work with PARE and other methods for SVs, ctDNA (BEAMing) #NGDx
5:28pm August 24th 2016 via Hootsuite
Velculescu: Shows a slide reviewing first 100 cancer genomes, by type, genes, regions, sequence volume, and references #NGDx16
5:25pm August 24th 2016 via Hootsuite
Victor Velculescu (Johns Hopkins): Liquid biopsy approaches for characterizing cancer genomes #NGDx16
5:22pm August 24th 2016 via Hootsuite
Stavis: Extraction kit may be biasing measurement; next can characterize this directly; extensible w/add'l colors/fluors #NGDx16
4:03pm August 24th 2016 via Hootsuite
Stavis: Concludes: 'new level of quantitative rigor'; inexpensive (relatively) at $100-200K; new comb of resolution, thru-pt #NGDx16
4:02pm August 24th 2016 via Hootsuite
Stavis: From their pt sample, looking at size distribution before/after Rx, measuring thousands of molecule's size dist #NGDx16
3:59pm August 24th 2016 via Hootsuite
Stavis: Now with 500bp synthetic DNAs, shows unpublished favorable CVs. #NGDx16
3:56pm August 24th 2016 via Hootsuite
Stavis: Showed potential for imaging thousands of molecules in short timeframe. Able to reduce photon signal to fluorescence #NGDx16
3:54pm August 24th 2016 via Hootsuite
Stavis: Decided to combine methods; shows DNA size not resolved from ctDNA from a cancer pt where sample collection was easy #NGDx16
3:51pm August 24th 2016 via Hootsuite
Stavis: Another method - fluorescence fluctuation; hithruput, complex, low res below 1000bp. https://t.co/Hmtm1KaMJW #NGDx16
3:48pm August 24th 2016 via Hootsuite
Stavis: There has been a lot of single-molecule biophysics in the past 20y. AFM, on a mica substrate. Hi-res, simple, low thrupt #NGDx16
3:45pm August 24th 2016 via Hootsuite
