tcga(the cancer genome atlas) catalogue genetic mutations responsible for cancer, using genome...
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TCGA(The cancer genome atlas)
• catalogue genetic mutations responsible for cancer, using genome sequencing and bioinformatics
• The TCGA is sequencing the entire genomes of some tumors, including at least 6,000 candidate
genes and microRNA sequences
2014The Somatic Genomic Landscape Of Chromophobe Renal Cell CarcinomaCancer Cell. Published online 21 Aug. 2014
Multiplatform Analysis of 12 Cancer Types Reveals Molecular Classification within and across Tissues of OriginCell. Published online 07 Aug. 2014
Comprehensive Molecular Characterization of Gastric Adenocarci-nomaNature. Published online 23 July 2014
Comprehensive molecular profiling of lung adenocarcinomaNature. Published online 09 July 2014
Comprehensive molecular characterization of urothelial bladder carcinomaNature. 507 (7492):315-22.
2013The Somatic Genomic Landscape of GlioblastomaCell. 155 (2):462-477.
Comprehensive molecular characterization of clear cell renal cell carcinoma.Nature. 499 (7456):43-49
Integrated genomic characterization of endometrial carcinoma.Nature. 497 (7447):67-73.
Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia.NEJM. 368:2059-2074
2012Comprehensive molecular portraits of human breast tumors.Nature. 490 (7418):61-70.
Comprehensive genomic characterization of squamous cell lung can-cers.Nature. 489 (7417):519:525
Comprehensive molecular characterization of human colon and rectal cancer.Nature. 487 (7407):330-337.
2011Integrated genomic analyses of ovarian carcinoma.Nature. 474 (7353):609-615.
2010Identification of a CpG Island Methylator Phenotype that Defines a Distinct Subgroup of Glioma.Cancer Cell. 17 (5):510-522
An integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR and NF1.Cancer Cell. 17 (1):98-110
2008Comprehensive genomic characterization defines human glioblas-toma genes and core pathways.Nature. 455 (7216):1061-1068
The Cancer Genome Atlas Research Network Publications
Development of the molecular classification of gastric cancer and to identify dys-
regulated pathways and candidate drivers of distinct classes of gastric cancer
Classification of gastic cancer
• Array-based somatic copy number analysis
: SNP-based copy number analysis
• Whole exome sequencing
• Array based DNA methylation profiling
• mRNA seq
• miRNA seq
• Reverse-phase protein array(RPPA)
Molecular platform
From 295 patient tumor sample
pa
Molecular characteristics of EBV-positive gastric cancers
pathseq algorithm
: human reference genome/ microbial reference genome(including bactorial, viral, archaeal, fungal)
RHOA(Ras homologue gene family, member A)
• Small GTPase protein known to regulate the actin cytoskele-ton
in the formation of stress fivers
• RhoA has been found to be hyper activated in gastric can-
cer
cells
• RHOA mutation were enriched in the genomically stable
subtype
(15% of genomically stable cases, p=0.0039)
• RhoA activity has been linked within several cancer ap-plications
due to its significant involvement in cancer signaling cascades
RHOA and ARHGAP6/26 somatic genomic alter-ations are recurrent in genomically stable gastric
cancer
Whole exome-seq(107 tumours) 5696 structural rearrangement(74 predicted, in-frame gene fusion)
De novo assembly of mRNA seq data 170 structural rearrangement
• ARHGAP26(GRAF)
GTPase-activating protein(GAP),
RHO GTPaseGDP
• CLDN78
Component of the tight junction
adhesion structure
RHOA and ARHGAP6/26 somatic genomic alter-ations are recurrent in genomically stable gastric
cancer