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AAV2 Virus May Be Linked to Hepatocellular Carcinoma in Patients With No History of Cirrhosis or Other Risk Factors

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Key Points

  • Hepatocellular carcinoma usually occurs in a liver that has already been damaged by, for example, excessive alcohol consumption, obesity, or chronic viral infection by hepatitis B or C viruses.
  • The integration of viral DNA was found more often in tumor cells than in healthy cells in the study participants.
  • Moreover, of the 11 patients tested, 8 did not have cirrhosis, and 6 of them presented with no known risk factors for liver cancer.

More than a cause of a simple infection, viruses are often involved in the development of serious diseases. Such is the case with liver cancer, which often develops in an organ that has been weakened by hepatitis B or C virus.

Researchers at Inserm, the Paris Public Hospitals (AP-HP), Paris Descartes University, Paris 13 University (USPC), and Paris Diderot University have identified the role of a new virus (adenoassociated virus type 2), previously unsuspected, in the occurrence of a rare type of liver cancer. The study, based on follow-up and observation of 193 patients, was published by Nault et al in Nature Genetics.

With over 8,000 new individuals diagnosed annually, liver cancer mainly affects men and is a major cause of death worldwide. Among the different types of liver cancer, hepatocellular carcinoma usually occurs in a liver that has already been damaged by illness. The liver may, for example, have been weakened by excessive alcohol consumption, obesity, or chronic viral infection by the hepatitis B or C viruses.

Patients with cirrhosis generally undergo regular tests to detect cancer. However, in 5% of cases, liver cancer occurs in patients who had not reported cirrhosis, and the reason for developing the cancer remains to be identified.

Study Findings

Jessica Zucman-Rossi, MD, PhD, and colleagues focused on these cirrhosis-free patients to determine the risk factors that had contributed to the development of their cancer.

In the genome of the tumor cells of 11 patients, the scientists observed the insertion of a viral DNA segment from adenoassociated virus type 2 (AAV2). This virus had previously been considered nonpathogenic for humans.

To confirm involvement of the virus in the cancer, the research team compared tumor tissues with normal tissues. The integration of viral DNA was found more often in tumor cells than in healthy cells in these 11 patients. Moreover, 8 of these patients did not have cirrhosis, and 6 of them presented with no known risk factors for liver cancer.

By studying these malignant cells in greater detail, they discovered that the virus, when inserting its DNA into the genome of the patient's cells, targets genes that are important in cell proliferation. This step leads to excessive expression of these genes, which, according to the researchers, may favor tumor development.

These results also call for caution: “AAV2 is often used as a vector in gene therapy. Although the insertion of its DNA into tumor promoting genes is rare, and probably a chance event, precautions must be taken regarding the use of this virus,” explained the authors.

Dr. Zucman-Rossi is the corresponding author of the Nature Genetics article.

This study was supported by the French National Cancer Institute and the French National Cancer League. 

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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