Robert Schreiber (Washington Univ, MO) “Using genomics to personalize cancer immunotherapy” RS #AACR15
11:12am April 19th 2015 via Hootsuite
SB: Targeting methylation for therapy: many types of therapies with many mechanisms '12 Nature Rev Genetics http://t.co/TYmDhtbSb2 #AACR15
11:05am April 19th 2015 via Hootsuite
SB: Cancers reprogram DNA methylation. Regions of focal hypermethylation & long-range hypometh. coincide '12: http://t.co/NwgNlaRyl3 #AA
10:58am April 19th 2015 via Hootsuite
SB: From '13 Cairns review http://t.co/KsXuaTMLG1 a-ketoglutarate dependency accumulates cytosine demethylation #AACR15
10:55am April 19th 2015 via Hootsuite
SB: #AACR15 figure of 4 cancer types. http://t.co/uUttldhQsU
10:54am April 19th 2015 via Hootsuite
SB: How we define the epigenome #TCGA. Colorectoal, Glioblastoma, Gastric, Kidney papillary: 100's of genes, CpG island phenotypes #AACR15
10:52am April 19th 2015 via Hootsuite
SB: Describes all epigenetic processes in an epic slide. #AACR15 http://t.co/DkGCWZuPuz
10:50am April 19th 2015 via Hootsuite
SB: 'Epigenetics is the software compared to the hardware of DNA' and can be changed. #AACR15
10:48am April 19th 2015 via Hootsuite
SB: Compares classic to modern def'ns of epigenetics: new phenotype w/o corresponding change in DNA sequence. #AACR15
10:46am April 19th 2015 via Hootsuite
Stephen Baylin (Johns Hopkins) “Above the genome: the epigenome and its biology and translational potential” SB #AACR15
10:45am April 19th 2015 via Hootsuite
TJ: (IMHO he was about 20% too fast for me to capture 40% more of his references. Oh well.) #AACR15
10:44am April 19th 2015 via Hootsuite
TJ: Concl: very optimistic. 'If you get the sense that CRISPRs are everywhere, that they are changing the landscape, you are right" #AACR15
TJ: Not just lung ca, others on pancreas. Future: multiplexing with 2 sgRNAs. Dec '14 Nature ref http://t.co/GZgOZfgQop #AACR15
10:43am April 19th 2015 via Hootsuite
TJ: From mice to isogenic cell lines for CRISPR based and chemical screens, then do functional models, quick testing #AACR15
10:41am April 19th 2015 via Hootsuite
TJ: Dep on gene and site, can observe different things. Introducing Nrf2 muts elsewhere, inh lung tumorigenesis #AACR15
10:40am April 19th 2015 via Hootsuite
TJ: Point muts in Nrf2: point muts disrupt Nrf2-Keap1 interaction. sgRNA by accident hit the same region. Finding deletions, up-reg #AACR15
10:39am April 19th 2015 via Hootsuite
TJ: LOF mutations in Keap1 - confirming role as a TS gene. Nrf2 doesn't have a good reagent for detection; showed downstream target #AACR15
10:38am April 19th 2015 via Hootsuite
TJ: Keap1-Nrf2 pathway - cell resp to oxidation stress. Background '11 Nature http://t.co/bQgk4TDwJr Keap1 loss accel. tumor form #AACR15
10:37am April 19th 2015 via Hootsuite
TJ: A dominant neg mutation, dependent on the gene and nature of sgRNA binding. #AACR15
10:33am April 19th 2015 via Hootsuite
TJ: 100's of tumors, done in 6mo. "Would have taken 4-5y, and ? dollars'" Showed loss-of-fn in PTEN selected, large del Nkx2.1 #AACR15
10:32am April 19th 2015 via Hootsuite
TJ: Bifunctional somatic mutations - inactivate tumor supressors. All three worked 'within 10 w' '14 Nature http://t.co/uOl3sp4Fyx #AACR15
10:31am April 19th 2015 via Hootsuite
TJ: Fast, inexpensive, and efficient. GOF: beta-catenin gene. Included 4b change; liver cells show b-catenenin expressed #AACR15
10:29am April 19th 2015 via Hootsuite
TJ: They use CRISPR for functional analysis of cancer genes in mice liver. Nature '14 http://t.co/YFgqA0I6i0 PTEN and other genes #AACR15
10:28am April 19th 2015 via Hootsuite
TJ: Intro to CRISPR-Cas. Now 1300 papers since Doudna papers 2y ago. Many pubs. Can do indel muts, turn on genes, mice KO/KI #AACR15
10:26am April 19th 2015 via Hootsuite
TJ: Lists 3 #TCGA studies of lung ca - many mutations. 18 in this recent Nature ref http://t.co/znmdjfB3qm 'Then the clouds parted' #AACR15
10:24am April 19th 2015 via Hootsuite
TJ: Their work on programmed neoantigen expression 2011 ref http://t.co/UvWs0d32KW and endogenous T-cell responses #AACR15
10:21am April 19th 2015 via Hootsuite
TJ: Quickly reviews genome engineering in cancer, from c-Myc to Ras to TP53 and cre lentiviral vectors. cDNA, miRNA, shRNA exp. #AACR15
10:19am April 19th 2015 via Hootsuite
Tyler Jacks (Koch Inst, MIT) “Engineering the cancer genome” TJ #AACR15
10:16am April 19th 2015 via Hootsuite
MS: Others sig's: 'we have no idea'. Add'l cancer analyses may reveal it. Mutagenesis, defective DNA repair - a catalog may be built #AACR15
10:14am April 19th 2015 via Hootsuite
MS: Large chart of ~35 sigs: 5meC deamination, shows tobacco, UV, aflatoxin, aristolochic acid (makes wild # of genomes) etc. #AACR15
10:13am April 19th 2015 via Hootsuite
MS:Overexp. of APOBEC in yeast - kataegis generated. dsDNA breaks nucleates kataegis in yeast. #AACR15
10:11am April 19th 2015 via Hootsuite
MS: Different sample - one type of mut (sig.) much closer (100bp instead of 1Mb away). Other sample - multiple locations #AACR15
10:10am April 19th 2015 via Hootsuite
MS: Localized hypermutation called kataegis, Greek 'Thunderstorm'. Foci of subst - chart of 3K muts, distance ~1MB apart (random) #AACR15
10:09am April 19th 2015 via Hootsuite
MS: Is sig 2&13 collateral damage to retrotransposons? Cervical ca - lots of sig 2&13, indicates viral invasion. Liver: no sig 2/13.
10:08am April 19th 2015 via Hootsuite
MS: Cancer sig's 2&3: a family of APOBEC1/3A/3B. Which of 3 not known. The switch? No overexp of APOBEC. Could it be inflammation? #AACR
10:06am April 19th 2015 via Hootsuite
MS: AID: somatic hypermutation for Ig switch loci. APOBEC3A-H, mutate HIV, EBV, Retrotransposons, restricting their activity #AACR15
10:05am April 19th 2015 via Hootsuite
MS: AID/APOBEC are cytidine deaminases; C>U that is removed by DNA repair to T. If abasic - polymerase reverts to 'G'. #AACR15
10:04am April 19th 2015 via Hootsuite
MS: Sig 13 is C>G, both similar is preceded by a T base. In literature - patterns ass'd with mutagenic enzyme AID/APOBEC #AACR15
10:03am April 19th 2015 via Hootsuite
MS: For br ca - signature 2 and 13 account for 10%, and 'overwhelm with huge # of mutations of this type' Sig 2 C>T context spec #AACR15
10:02am April 19th 2015 via Hootsuite
MS: Will be focusing on 2 of the 30 signatures. Shows distribution across Br ca genomes, and contribution of the 30 sigs #AACR15
10:00am April 19th 2015 via Hootsuite
MS: 30 mutational signatures by cancer type #AACR15 http://t.co/4jdJRbad4v
RT @weldeiry: Dr Stratton describes life history of mutations as they contribute to a formed tumor #aacr15 http://t.co/YSI1Nz6tv1
9:57am April 19th 2015 via Hootsuite
MS: Six signatures, 96 possible base-before/after, 12K types, come up with 30 signatures, 30 diff processes #AACR15
9:56am April 19th 2015 via Hootsuite
MS: 8M somatic mutations, apply non-negative matrix factorization (NMF), and derive the landscape #AACR15
9:55am April 19th 2015 via Hootsuite
MS: Describing C>T in 16 contexts (one base before & after), now 96 mutation classes. From 12,023 cases, 40 ca types #AACR15
MS: 2002 paper ref http://t.co/DMOtg8YwLw of the math involved - on the 'parts of objects' to assist in math of classification #AACR15
9:54am April 19th 2015 via Hootsuite
MS: Challenge: from the end genome and determine what processes have been (different carcinogens, different times) Reduced to math #AACR15
9:53am April 19th 2015 via Hootsuite
MS: Pie chart of 6 substitutions: diff. in skin than lung. From egg to cancer cell: effect of carcinogens on distribution of sig's #AACR15
9:52am April 19th 2015 via Hootsuite
MS: Mutational processes is from cancer genomes; in the 80's it was TP53. Only looking at subst.: Of six (C-> T->) C>T skin #AACR15
9:49am April 19th 2015 via Hootsuite
MS:Somatic mutations occur in all cells throughout the body throughout life. "Our DNA is constantly under assault" #AACR15
9:47am April 19th 2015 via Hootsuite
