Note for: Genetics of Opisthorchis viverrini-related cholangiocarcinoma

Paper: Genetics of Opisthorchis viverrini-related cholangiocarcinoma
(doi: 10.1097/MOG.0000000000000162)

Aim:

Looking at the genetic, epigenetic, and transcriptional landscape of CCA

Method;

whole exome sequencing and target sequencing

Finding;

CCA-related genes mutations

TP53

KRAS

SMAD4

novel CCA-related genes mutations

chromatin remodeling

BAP1

ARID1A

MLL3

IDH1/2

Wnt-signaling

RNF43

PEG3

KRAS/G-protein

GNAS

ROBO2

OV and non-OV related;

Set of gene mutations  are different which may link to different pathogenesis of CCA

Adult Ov can stay at the biliary tract and remain in host for 10 years

Important risk factor for CCA;

Chronic inflammation in biliary tract epithelia

Epigenetic changes for Ov-related;

Hypermethylation of hMLH1 promoter (44.6%) -- reduced expression  and function (to me no surprised why it affect the RNF43 mutations -- due to RNF43 has the microsatellite in the coding region which is prone to missense/nonsense mutations)

Three main mechanisms to disrupt the biliary epithelial

1.immunopathology

2.toxicity from excretory and secretory  molecules from parasite

3.feeding behavior from parasites

Studies were done in OV-related and Non OV-related (mark for me was that those two groups were from different continent; OV-related-Thai, non OV-related Japanese). They show different mRNA profilling which related to etiology.

Inflammation leading to DNA damage and genetic changing, causing the transformation from normal to cancer cell.

Each square represents the sample, black – mutation, white – without mutation. All mutations have been found can be categorized into 7 groups according to the biological processes or pathways.

Factors contribute to mutation landscape (as observed);

1.etiology

2. host (how the host response toward the etiologic agent)

3. exposure period (short, long, frequency)

These key points make it very simple for this article what the team found.