My note on paper: Exome sequencing of liver fluke-associated cholangiocarcinoma
Paper: Exome sequencing of liver fluke-associated cholangiocarcinoma
(doi: 10.1038/ng.2273)
Point out only the points that I have been interested.
Whole exome sequencing: Expected result;
-provide insight into mutational landscape contributing to OV-CCA
-8 OV-related tumors and matched normal tissue
*206 somatic mutations in 187 genes
-validate bySangerr sequencing in another 46 cases (prevalent set) to detect recurrently mutated genes (15 genes)
Known cancer-related genes:
*TP53 -- 44.4%
*KRAS -- 16.7%
SMAD4 -- 16.7%
Somatic mutation in newly identified genes;
inactivation mutations
*MLL3 -- 14.85%
*ROBO2 -- 9.3%
*RNF43 -- 9.3%
*PEG3 -- 5.65%
activating mutation
GNAS -- 9.3%
These group of gene mutations can be divided;
1. deactivation of histone modifiers
2. activation of G protein signaling
3. loss of genome stability
Intro:
CCA -
*account for 10-25% of all primary liver cancers
*western -- 1.5/100,000 in western countries (age-standardized incidence rates - ASRs)
*dominant of liver cancer - northeastern Thailand and neighboring Loas and Cambodia (ASR -- 94.8-39.4/100,000)
Database
1. Genome MUtation Significance In Cancer (MUSiC)
2. Catalogue of Somatic Mutation in Caner (COSMIC)
PDAC = pancreatic ductal adenocarcinoma
TP53 = p53
*role in maintaining genomic stability
*RNF43 and PEG3 regulates p53
*functional disruption of p53, RNF43, PEG3 affect on genomic stability.
---
*SNP in RNF43 (rs2257205) -- associated with increased risk of pancreatic cancer in Japanese population
*In CCA exome sequencing; RNF43 somatic mutation - 2/5 nonsense, 3/5 missense (predicted by Polyphen)
RNF43 mutation showed poorer survival, might serve an independent predictive factor for survival
PEG3 - maternal imprinted gene, induce apoptosis through interaction with Siah1a (E3-Ub)
CCA shares common similarity in chromosonal aberration patterns with PDAC (pancreatic ductal adenocarcinoma) than HCC
Molecular level,
CCA and PDAC -- mutation spectra have more in common, suggested common pathway to tumorigenesis
Genetic alterations of GNAS, RNF43, ROBO2, PEG3 and XIRP2 - unique to CCA
(doi: 10.1038/ng.2273)
Point out only the points that I have been interested.
Whole exome sequencing: Expected result;
-provide insight into mutational landscape contributing to OV-CCA
-8 OV-related tumors and matched normal tissue
*206 somatic mutations in 187 genes
-validate bySangerr sequencing in another 46 cases (prevalent set) to detect recurrently mutated genes (15 genes)
Known cancer-related genes:
*TP53 -- 44.4%
*KRAS -- 16.7%
SMAD4 -- 16.7%
Somatic mutation in newly identified genes;
inactivation mutations
*MLL3 -- 14.85%
*ROBO2 -- 9.3%
*RNF43 -- 9.3%
*PEG3 -- 5.65%
activating mutation
GNAS -- 9.3%
These group of gene mutations can be divided;
1. deactivation of histone modifiers
2. activation of G protein signaling
3. loss of genome stability
Intro:
CCA -
*account for 10-25% of all primary liver cancers
*western -- 1.5/100,000 in western countries (age-standardized incidence rates - ASRs)
*dominant of liver cancer - northeastern Thailand and neighboring Loas and Cambodia (ASR -- 94.8-39.4/100,000)
Database
1. Genome MUtation Significance In Cancer (MUSiC)
2. Catalogue of Somatic Mutation in Caner (COSMIC)
PDAC = pancreatic ductal adenocarcinoma
TP53 = p53
*role in maintaining genomic stability
*RNF43 and PEG3 regulates p53
*functional disruption of p53, RNF43, PEG3 affect on genomic stability.
---
*SNP in RNF43 (rs2257205) -- associated with increased risk of pancreatic cancer in Japanese population
*In CCA exome sequencing; RNF43 somatic mutation - 2/5 nonsense, 3/5 missense (predicted by Polyphen)
RNF43 mutation showed poorer survival, might serve an independent predictive factor for survival
PEG3 - maternal imprinted gene, induce apoptosis through interaction with Siah1a (E3-Ub)
CCA shares common similarity in chromosonal aberration patterns with PDAC (pancreatic ductal adenocarcinoma) than HCC
Molecular level,
CCA and PDAC -- mutation spectra have more in common, suggested common pathway to tumorigenesis
Genetic alterations of GNAS, RNF43, ROBO2, PEG3 and XIRP2 - unique to CCA
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