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 23 February 2018

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News

Genetic features of aflatoxin-associated liver cancer

This month's issue of Gastroenterology investigates the genetic features of aflatoxin-associated HCC that can be used to differentiate them from HCCs not associated with this carcinogen.

News image

Dietary exposure to aflatoxin is an important risk factor for hepatocellular carcinoma (HCC).

However, little is known about the genomic features and mutations of aflatoxin-associated HCCs compared with HCCs not associated with aflatoxin exposure.

Dr Yi-Xin Zeng and colleagues from China investigated the genetic features of aflatoxin-associated HCC that can be used to differentiate them from HCCs not associated with this carcinogen.

The researchers obtained HCC tumor tissues and matched non-tumor liver tissues from 49 patients, collected from 1990 through 2016, at the Qidong Liver Cancer Hospital Institute in China—a high-risk region for aflatoxin exposure.

Somatic variants were identified using GATK Best Practices Pipeline.

The research team validated part of the mutations from whole-genome sequencing and whole-exome sequencing by Sanger sequencing.

The team also analyzed genomes of 1072 HCCs, obtained from 5 datasets from China, the United States, France, and Japan.

Mutations in 49 aflatoxin-associated HCCs and 1072 HCCs from other regions were analyzed using the Wellcome Trust Sanger Institute mutational signatures framework with non-negative matrix factorization.

The mutation landscape and mutational signatures from the aflatoxin-associated HCC and HCC samples from general population were compared.

The researchers identified genetic features of aflatoxin-associated HCC, and used these to identify aflatoxin-associated HCCs in datasets from other regions.

Tumor samples were analyzed by immunohistochemistry to determine microvessel density and levels of CD34 and CD274.

The researchers found that aflatoxin-associated HCCs frequently contained C>A transversions, the sequence motif GCN, and strand bias.

In addition to previously reported mutations in TP53, the team found frequent mutations in the adhesion G protein−coupled receptor B1 gene (ADGRB1), which were associated with increased capillary density of tumor tissue.

The team observed that aflatoxin-associated HCC tissues contained high-level potential mutation-associated neoantigens, and many infiltrating lymphocytes and tumors cells that expressed PD-L1, compared to HCCs not associated with aflatoxin.

Of the HCCs from China, 10% contained the aflatoxin-associated genetic features, whereas less than 1% to 4% of HCCs from other regions contained these genetic features.

Dr Zeng's team concludes, "We identified specific genetic and mutation features of HCCs associated with aflatoxin exposure, including mutations in ADGRB1, compared to HCCs from general populations."

"We associated these mutations with increased vascularization and expression of PD-L1 in HCC tissues."

"These findings might be used to identify patients with HCC due to aflatoxin exposure, and select therapies."

Gastroenterol 2017: 153(1): 249–262.e2
21 July 2017

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