National / Science & Health

Massive whole-genome study finds six types of liver cancer

by Tomoko Otake

Staff Writer

In the largest genomic study ever targeting single-organ cancers, Japanese researchers have completed a whole-genome analysis of 300 liver cancer patients, discovering that liver cancer among Japanese can be broken down into six types.

The study, jointly carried out by a number of institutions including the National Cancer Center, the Riken research institute and the University of Tokyo, hopes to contribute to the development of new diagnostic methods and personalized drug therapies.

In a paper published Tuesday in the journal Nature Genetics, the researchers extracted DNA and RNA from blood samples of 300 liver cancer patients and put them through next-generation genome sequencers, identifying a wide variety of mutations that have taken place.

To analyze the vast genomic data — totaling more than 300 terabytes — the scientists used Shirokane, a supercomputer used specifically for life science research at the University of Tokyo.

The study found that liver cancer is caused by mutations or abnormalities in nearly 40 genes, including more than 10 that had never before been linked to liver cancer. Depending on the mix of these factors, types of liver cancer among Japanese can be divided into roughly six types.

The research also found that the five-year disease-free survival rate ranged from zero to 80 percent, with patients with mutations in cancer-suppressor gene TP53 likely to suffer the most severe outcomes.

These findings could contribute to the development of new drugs that target key molecules involved in cancer cell growth, called molecular target therapy. Furthermore, patients might one day be able to choose therapies based on their genomic characteristics, according to Hidewaki Nakagawa, a Riken researcher involved in the project.

“There are not a whole lot of molecular target therapy options for liver cancer patients,” Nakagawa said by phone Tuesday. “Right now, we have only one such drug approved, called Sorafenib, but whether the drug is effective or what molecule it actually targets is not really known.

“The whole-genome analysis could change that, paving the way for personalized medicine.”

The team’s work is part of an international initiative called the International Cancer Genome Consortium (ICGC)/The Cancer Genome Atlas (TCGA). The ICGC/TCGA aims to coordinate large-scale cancer genome studies involving 50 different cancer types and subtypes.

“The fact that we have contributed 300 cases out of a total of 2,800 cases handled by the ICGC/TCGA shows the impact of this study,” Nakagawa said.

According to National Cancer Center statistics, liver cancer is the third-largest cause of cancer death among men in Japan and the sixth-largest among women. It kills more than 30,000 Japanese annually.