Durso: EML4-ALK gene expression visualization - colors indicate relative expression (high-low); EML4 expression turns on w/ALK #AMP2015
12:13pm November 6th 2015 via Hootsuite
Durso: Found 100% (24/24) fusions; Chimerascan most sensitive (23/24). deFuse and SOAPfuse detected the one missed #AMP2015
12:12pm November 6th 2015 via Hootsuite
Durso: 25 samples w/known fusions (15 frozen thyroid, 3 marrow, 7 FFPE lung) Reviews yield and seq metrics. FFPE very comparable #AMP2015
12:11pm November 6th 2015 via Hootsuite
Durso: Similar categorization scheme: I are known from db's; II from allOnco db; III supporting reads #AMP2015
12:08pm November 6th 2015 via Hootsuite
Durso: Pipeline all open source: FASTQC, TopHat, Piccard; Chimerascan, DeFuse, FusionChecker #AMP2015
12:07pm November 6th 2015 via Hootsuite
Durso: Goal - FFPE vs fresh frozen; RIN score for frozen, >200bp for FFPE RNA. Used ILMN stranded total RNA for library. #AMP2015
12:06pm November 6th 2015 via Hootsuite
Durso: Targeted RNA NGS useful for known fusions, but whole transcriptome enables discovery, also gene exp. #AMP2015
12:05pm November 6th 2015 via Hootsuite
Mary Beth Durso (Univ Pittsburgh) Dev of clinical transcriptome analysis for detection of fusions and gene expression in oncology #AMP2015
12:04pm November 6th 2015 via Hootsuite
Reuther:Q:More about the class III? A:Manual review based upon tumor type; also diagnostic utility of class II can be moved to I #AMP2015
12:03pm November 6th 2015 via Hootsuite
Reuther: 42% were class I, 9% class II (over 50%) from their 21 unknown samples #AMP2015
12:02pm November 6th 2015 via Hootsuite
Reuther: Example: CIC-FOXO4, very rare, only 2 other cases in malignant sarcoma. Unexpected: MLL-MLLT10 (usu. infantile leukemia) #AMP2015
12:00pm November 6th 2015 via Hootsuite
Reuther: From Cat I/II: showed data cp against FISH, RT-PCR, Panel, and whole-transcriptome. 38% better than FISH #AMP2015
11:58am November 6th 2015 via Hootsuite
Reuther: Reviews their clinical classification rules: I diagnostic fusion; II targetable; III cancer-associated; IV 'other' #AMP2015
11:56am November 6th 2015 via Hootsuite
Reuther:. ID'd from the 7304, 184 fusions. 7 median fusions/case. For Ewings in their validation set, 5 novel discovered #AMP2015
11:54am November 6th 2015 via Hootsuite
Reuther: Can use as little as 20ng. 20 ped sarcomas; 7.3k calls; 1.4k inter- and intra-chrom calls; transcription-induced chimaras #AMP2015
11:53am November 6th 2015 via Hootsuite
Reuther: VIF calls every clinically sig fusions, regardless of seq quality. Use both capture RNA-Seq as well as whole transcriptome #AMP2015
11:52am November 6th 2015 via Hootsuite
Reuther: STAR used for alignment to ref genome; used deFuse for fusion calling, 'VIF pull-through' via COSMIC #AMP2015
11:51am November 6th 2015 via Hootsuite
Reuther: GFUS - gene fusions of unknown sig. On sarcomas - 9 for training, 4 known, 21 unk. 89M PE HiSeq reads/smpl #AMP2015
11:50am November 6th 2015 via Hootsuite
Jacquelyn Reuther (Baylor TX) "Diagnostic yield of RNA seq in the det of pathogenic fusion in childhood sarcomas of uncertain dx" #AMP2015
11:49am November 6th 2015 via Hootsuite
Omics! Omics!: Comments on "The use and misuse of supplementary material in science publications" https://t.co/APoDu3Gk2h
9:15am November 6th 2015 via Hootsuite
Nadauld:Q: How is a MTB paid for? A:A challenge, not reimbursed. People do it to gain experience (job desc!) 4-5 people - feasible. #AMP2015
8:55am November 6th 2015 via Hootsuite
Nadauld: For the MTB - a cell biologist who understands signalling 'can also be helpful'; remote technology used as well #AMP2015
8:48am November 6th 2015 via Hootsuite
Nadauld: Young breast ca pts - reflex to germline testing. Have found 4 families - BRCA, Lynch, Li-Fraumeni, even p16 #AMP2015
8:47am November 6th 2015 via Hootsuite
Nadauld: "I'm happy every day we set this up, because it (MTB) provides so much value" #AMP2015
8:45am November 6th 2015 via Hootsuite
Nadauld: But in this case - blood-brain barrier a problem, melanoma spread. #AMP2015
8:44am November 6th 2015 via Hootsuite
Nadauld: Scans after 9mo: 'surprising response'. Did well for 18 mos. Case 3: met melanoma, 52yo, found cKIT. Showed 8mo progress #AMP2015
Nadauld: So now they start genomic profiling earlier, to change std treatment earlier. Had BRAF mut (not V600E), on MEKi #AMP2015
8:42am November 6th 2015 via Hootsuite
Nadauld: Case 2: 56yo, met lung ca: prog. thru std chemotherapy. Often timeframe for genomic testing means therapy not option #AMP2015
Nadauld: Anecdote 2: He still passed away, but 5 kids, daughter 16 said "he saw my first boyfriend... and my first breakup." #AMP2015
8:40am November 6th 2015 via Hootsuite
Nadauld: Anecdote: Pt says, "A disaster has happened; my cellphone plan was cancelled b/c I wasn't planning on living this long." #AMP2015
8:39am November 6th 2015 via Hootsuite
Nadauld: Showed serial CT scans, dramatic progress over 4 months 'near complete response'. Lasted 15 months, survived 2y post-test #AMP2015
8:38am November 6th 2015 via Hootsuite
Nadauld: mCRC case: multiple treatments, no other treatment options, 40yo. After analysis: HER2 ampl. (happens in 3% of CRC) #AMP2015
Nadauld: Cost of drug for targeted Rx much higher, but equivalency due to fewer admissions, adverse events. Remarkable. #AMP2015
8:37am November 6th 2015 via Hootsuite
Nadauld: But results - Progression Free Survival (PFS) was longer with targeted. (n=195) b/c they had the data. Cp costs: same! #AMP2015
8:36am November 6th 2015 via Hootsuite
Nadauld: Cohort study of 195 - 41 w/o mut; 79 no receipt of targeted Rx. Of the 75: 39 w/o match, results to be published soon #AMP2015
8:35am November 6th 2015 via Hootsuite
Nadauld: Asking the hard questions - b/c these CNAs are actionable. #AMP2015
8:34am November 6th 2015 via Hootsuite
Nadauld: HRAS, DDR2, HVL, PIK3CA... May sound overwhelming, but this is 'where molecular pathologists play a vital role' #AMP2015
Nadauld: For CNA: Venn is discordant rate, validated via FISH for CNA. Their 94% vs 48% concordant, high FN rate on other assay #AMP2015
8:33am November 6th 2015 via Hootsuite
Nadauld: Note on CNA's "Not all platforms are equivalent". Many hotspot tests; showed Venn of 40% overlap, but 48% unique to ICG100 #AMP2015
8:31am November 6th 2015 via Hootsuite
Nadauld: Compared though to the Molecular Tumor Board, the distribution shifts. KRAS, ATM, BRCA2, PTEN, NRAS... #AMP2015
Nadauld: Provider is looking for other treatment options, 'worked very well'. Busy pie chart of list of actionable var's. #AMP2015
8:30am November 6th 2015 via Hootsuite
Nadauld: Impact: 41% immediate change, 38% prospective change (due to treatment progression). n=195. 'Really surprised us' #AMP2015
Nadauld: Example ICG100 Test Report: Gene RET, recommended Rx; second gene PTEN, two therapies #AMP2015
8:29am November 6th 2015 via Hootsuite
Nadauld: Partner N of One gives context, interpretation and supporting evidence. Distilling down var's to their interpretation #AMP2015
8:27am November 6th 2015 via Hootsuite
Nadauld: Reviews a sample list - 'like Greek to the physician'. ("What do you do wiht a NOTCH1?") #AMP2015
Nadauld: A consensus 'and I'm surprised how often it happens'. Most lists of var's have pretty clear treatment options. #AMP2015
8:25am November 6th 2015 via Hootsuite
Nadauld: Worried about VUS and long lists of var's; their board is multi-inst, experts in cancer genomics; one photo had 18 people #AMP2015
8:24am November 6th 2015 via Hootsuite
Nadauld: Use DNANexus, system called Sciops, E-portal for ordering/results delivery. https://t.co/MuiX8fbBY9 (a non-profit) #AMP2015
8:23am November 6th 2015 via Hootsuite
Nadauld: Workflow slide - just like others! - 14-15 day TAT. Their molecular tumor board impt part. Work with Toma for assay #AMP2015
8:22am November 6th 2015 via Hootsuite
Nadauld: In-house testing is feasible: control of data, turnaround time, and costs. Others may decide not to. #AMP2015
8:20am November 6th 2015 via Hootsuite
