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

Define of a molecular subtypes of gastric cancerSCNA : somatic copy number aberration

pa

Molecular characteristics of EBV-positive gastric cancers

pathseq algorithm

: human reference genome/ microbial reference genome(including bactorial, viral, archaeal, fungal)

Significantly mutated genes in non-hypermutated gastric cancer

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

Integrated molecular description of gastric cancer

Key features of gastric cancer subtype