WASHINGTON, Nov. 3, 2013 /PRNewswire/ -- Although very rare, the use of oral contraceptive can lead to benign tumors in the liver. The tumors, known as hepatocellular adenomas, can become malignant. It is, however, difficult for physicians to assess the risk of these tumors becoming malignant.
The study's researchers examined and classified data from 250 patients with hepatocellular adenomas. They examined classical adenomas (223), borderline lesions between adenomas and carcinomas (18), and carcinomas (9). The data was examined using whole exome sequencing, CGH-SNP analyses, and methylome analyses.
Researchers were able to identify the genetic determinants of malignant transformation as well as the key factors at stages of the transformation. "Our work reported for the first time a molecular mechanism of malignant transformation of hepatocellular adenomas to carcinomas," lead researcher, Camilla Pilati, PhD, said, "Surprisingly, we were able to identify the chronology of the genetic defects that accumulate in hepatocytes to promote their malignant transformation. In this line, we identified genetic alteration that acts at early and late steps of the malignant transformation process, in the accumulation of early genetic alteration at the origin of the malignant transformation of the hepatocytes."
Two genes with somatic mutations -- one in the early stages and one in the later stages -- were identified in the malignant transformation. Mutations of beta-catenin are associated with many forms of cancer, and beta-catenin activation and TERT promoter mutations in the early and later stages, respectively, were identified in the malignancy process. In addition, the researchers were able to identify factors that determined adenomas that were not at a high risk of becoming carcinoma.
"This work provided new insights about the major genetic determinants of malignant transformation and their timeframe accumulation during the adenoma-carcinoma sequence. At the clinical level, we believe that these results open new avenues for personalized medicine in hepatocellular adenomas," said Dr. Pilati.
"The aim of this classification is the identification of new biomarkers useful for a more precise diagnosis and that could be used as therapeutic targets. This is clearly an important step to develop a more personalized medicine with, for example, the selection of patients with high risk of malignant transformation that require a specific follow-up and more radical treatment," Dr. Pilati concluded. "Identification of CTNNB1 and TERT promoter mutation as key genetic determinants of malignant transformation in HCA will be useful to propose tailored treatment in these subtypes of patients.
Integrative genomic profiling of hepatocellular adenomas identify mutational processes involved in malignant transformation.
AASLD is the leading medical organization for advancing the science and practice of hepatology. Founded by physicians in 1950, AASLD's vision is to prevent and cure liver diseases. This year's Liver Meeting®, held in Washington, November 2-5, will bring together more than 9,000 researchers from 55 countries.
A pressroom will be available from November 1 at the annual meeting. For copies of abstracts and press releases, or to arrange researcher interviews, contact Gregory Bologna at 703-299-9766.
Press releases and all abstracts are available online at www.aasld.org.
Media Contact: Gregory Bologna
Press Room: November 1 – 5, 2013
Walter E. Washington Convention Center, Washington, DC
Researcher: Camilla Pilati, PhD
Phone: 0033 1 53725193
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|SOURCE American Association for the Study of Liver Diseases (AASLD)|
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