Lawrence Jennings (Childrens Hosp Chicago IL) AMP/Cap guidelines for validation of NGS-based oncology panels #AMP2017

1:37pm November 18th 2017 via Hootsuite

Li: Went through three detailed case studies in Dx. Last was a novel EWSR1-CREB3L3 fusion, ended up w/radical mandible resection #AMP2017

1:35pm November 18th 2017 via Hootsuite

Li: change of gears: CHOP NGS Panel description: large for solid, heme, fusion and hereditary. All coding flanking 10bp#AMP2017

1:27pm November 18th 2017 via Hootsuite

Li: Other rec's: clear desc of clin sig; clear desc of confirmation methods. Ref J Mol Diagn '17 https://t.co/Noyq5Y9Fzv #AMP2017

1:26pm November 18th 2017 via Hootsuite

Li: Var nomenclature: Gene name; Transcript ID accession and ver number; nucleotide change; aa change; VAF; coord's… https://t.co/hbf4qTb76H

1:24pm November 18th 2017 via Hootsuite

Li: Shows a few examples of older / newer classification. Recommend 4-tier reporting, only 1-3 to physician. #AMP2017

1:22pm November 18th 2017 via Hootsuite

Li: Germline in tumor testing: Consider gene char - tumor supp or oncogene; pt information, family history etc #AMP2017

1:20pm November 18th 2017 via Hootsuite

Li: Tier IV benign / likely benign. Find germline vars in tumor testing: var freq usu 50% for germline. But CNVs mu… https://t.co/F8t8Spm5U1

1:19pm November 18th 2017 via Hootsuite

Li: Ex of Tier III, vars of unk sig, showed on dbSNP entry, low freq, controversial via SIFT and other tools #AMP2017

1:16pm November 18th 2017 via Hootsuite

Li: Tier II: fusion in Ph-like ALL, GENEA1-JAK2. No drug, in pediatric case, no guidelines at present. db's don't apply. #AMP2017

1:15pm November 18th 2017 via Hootsuite

Li: (Tier III/IV have insufficient evidence, a matter of degree.) Tier I examples: EGFR exon 14 18bp inframe del, shows chart #AMP2017

1:13pm November 18th 2017 via Hootsuite

Li: Tier II evidence is var's of potential clin significance. Level C/D. #AMP2017

1:11pm November 18th 2017 via Hootsuite

Li: Evidence-based char: Tier I vars have strong clinical significance, includes Level A and Level B evidence. #AMP2017

1:10pm November 18th 2017 via Hootsuite

Li: Dx/Prog for Lvl D: TP53 common muts, deletion of CDKN2A also. #AMP2017

1:09pm November 18th 2017 via Hootsuite

Li: Lvl D: Rx plausible preclin data derived from cell lines (in vitro) and animal models. Early Ph1 for safety. #AMP2017

1:08pm November 18th 2017 via Hootsuite

Li: Lvl C MDS-RS + SF3B1 mut good prognosis. #AMP2017

1:07pm November 18th 2017 via Hootsuite

Li: Lvl C Rx: Ph-like ALL: P2RY8-CRLF2 activates JAK-STAT, clin trial using JAKi. Lvl C Dx: spliceosome mutations #AMP2017

1:07pm November 18th 2017 via Hootsuite

Li: Pilocytic Astrocytoma - KIAA1549-BRAF -> good prognosis, level B evidence for prongnosis #AMP2017

1:05pm November 18th 2017 via Hootsuite

Li: Lvl B Dx: Cutaneous mastocytosis, others types ruled out. KIT D816V found in bone marrow of ~100% CM pts. #AMP2017

1:04pm November 18th 2017 via Hootsuite

Li: Level B vars: for Rx, very strong evidence, not FDA-approved. Hairy Cell Leuk: BRAF V600E ~100% response to vemurafenib #AMP2017

1:03pm November 18th 2017 via Hootsuite

Li: Leval A Dx: prof guidelines. Level A prognosis: also prof guidelines. In AML, FLT3-ITD -> poor prognosis #AMP2017

1:01pm November 18th 2017 via Hootsuite

Li: Level A Rx: FDA-approved biomarker for spec Rx; or predict response. Ex ALK mut predicts resistance #AMP2017

12:59pm November 18th 2017 via Hootsuite

Li: Grouped evidence to 4 levels: A-D, clinical and/or expt'l evidence. Therapeutics, diagnosis, prognosis. #AMP2017

12:58pm November 18th 2017 via Hootsuite

Li: Biomarker can alter fn of gene, can serve to include to trials, influence prognosis, est Dx, may warrant surveillance #AMP2017

12:57pm November 18th 2017 via Hootsuite

Li: Def'n of biomarkers: all vars are biomarkers, but not the other way around. Pred sens, resist. or toxicity to spec Rx #AMP2017

12:57pm November 18th 2017 via Hootsuite

Li: In '14 - Assembled multidisciplinary group Feb '15; May finished technical survey; June '16 std guidelines pub end of '16 #AMP2017

12:56pm November 18th 2017 via Hootsuite

Marilyn Li (Childrens Hosp Philadelphia PA) AMP/ASCO/CAP Stds and Guidelines of Somatic Variant Interpretation and Reporting #AMP2017

12:54pm November 18th 2017 via Hootsuite

Curious what @Pillar_Bio is up to for clinical oncology at #AMP2017 ? Here’s an interview for you. https://t.co/pnH6pQuY9F

12:50pm November 18th 2017 via Hootsuite

Hey #AMP2017 - Fran de Abreu (L) presenting @Pillar_Bio data at ST131 in the poster session happening now. https://t.co/EeCH760jsk

12:05pm November 18th 2017 via Hootsuite

Tadimety: Shows capture from 20-150 ng/mL mut and wt DNA binding, and peak wavelength. #AMP2017

9:45am November 18th 2017 via Hootsuite

Tadimety: Peak shifts from 900 empty, shows difference in peak from wt to mutKRAS bound. #AMP2017

9:44am November 18th 2017 via Hootsuite

Tadimety: Have gold nanorods with PNA that bind, and surface plasmon can detect on surface. Showed nanorod conj w/PNA w/mut G12V #AMP2017

9:43am November 18th 2017 via Hootsuite

Tadimety: Small scale is better sens / spec due to surface to volume, and conserving sample. Also can multiplex #AMP2017

9:41am November 18th 2017 via Hootsuite

Tadimety: Also Cellsearch CTC is used. Use of microchip biosensors: a recognition element; a transduction element; readout #AMP2017

9:39am November 18th 2017 via Hootsuite

Tadimety: PDAC - poor prognosis, difficult to diag, most Dx at adv stage, absence of spec symptoms. CT imaging, Pathway Genomics #AMP2017

9:39am November 18th 2017 via Hootsuite

Tadimety: Shows intro slides on liquid biopsies' usage, and focus on G12V in KRAK for PDAC (common mutation) #AMP2017

9:38am November 18th 2017 via Hootsuite

Amogha Tadimety (Dartmouth NH) TT24 Screening circ nucleic acids of pancreatic ductal adenocarcinoma using a plasmonic nanosensor #AMP2017

9:36am November 18th 2017 via Hootsuite

Q: At higher input (50ng) could 3 droplets be detected? Wood-Bouwens: Recommend increase replicates. >10ng, noisy data #AMP2017

9:34am November 18th 2017 via Hootsuite

Wood-Bouwens: Simple to perform, customizable; TAT from draw to data in <1d. Sens down to 0.1%. #AMP2017

9:32am November 18th 2017 via Hootsuite

Wood-Bouwens: 5 courses of treatment overlay - lower ctDNA counts; higher counts when off-Rx. #AMP2017

9:30am November 18th 2017 via Hootsuite

Wood-Bouwens: At day 154 - spike in ccfDNA but TP53 steady at 20 ctDNA per mL. Spike may be normal cell death due to chemo #AMP2017

9:29am November 18th 2017 via Hootsuite

Wood-Bouwens: Shows 182 d Rx course; and wt ccfDNA molecules/mL from 6K downt to 2K and day 154 spike. ctDNA/mL from 0 to 50. #AMP2017

9:28am November 18th 2017 via Hootsuite

Wood-Bouwens: Gemcitabine and cisplatin, monitoring TP53 E285K, and RPP30 (general ccfDNA quant to det tumor burden) #AMP2017

9:27am November 18th 2017 via Hootsuite

Wood-Bouwens: Better sens is from more DNA input. Now they have their first longitudinal pt - Pt has bile-duct ca TP53 p.E285K #AMP2017

9:26am November 18th 2017 via Hootsuite

Wood-Bouwens: Shows 1ng, 300 haploid equiv, only 3 KRAS G12D mutant molecules called. Shows expected and meas at 0.1% 10ng input #AMP2017

9:25am November 18th 2017 via Hootsuite

Wood-Bouwens: Basically a training set with a confidence interval. '17 ref called 'data gridding' https://t.co/c4yF1iP2QH #AMP2017

9:24am November 18th 2017 via Hootsuite

Wood-Bouwens: High density droplets - clustering is clear. Low conc, hard to cluster. Uses a mixed ca cell line, with 50% mutants. #AMP2017

9:23am November 18th 2017 via Hootsuite

Wood-Bouwens: The longer amplicon can then be differentiated between empty, wild type, and mutant products. #AMP2017

9:22am November 18th 2017 via Hootsuite

Wood-Bouwens: Looking for dual allele - with reverse primers. Each droplet has all 3 primers; mutant allele primer has AAAT repeats #AMP2017

9:21am November 18th 2017 via Hootsuite

Wood-Bouwens: Single-color: forward primer is matches; genotyping reverse is perfect match or mutant. +/- amplicons #AMP2017

9:21am November 18th 2017 via Hootsuite