Page 105 - Read Online

Ma et al. Hepatoma Res 2019;5:8 I http://dx.doi.org/10.20517/2394-5079.2018.104 Page 9 of 12

while it remains challenging to target TERT gene, new strategies are emerging to achieve this goal and make
more effective therapy possible.

CONCLUSION
Our knowledge regarding the role of TERT promoter mutations in HCC is expanding; nevertheless, there
remain many puzzles to be solved. Although the pattern of TERT promoter mutations in HCC is well-
established, little is known about the mechanism through which TERT promoter mutations reactivate
telomerase and promote tumor development. We are not yet sure how either somatic mutations or HBV
integrations in the TERT promoter lead to malignant transformation and whether they can be prognostic
biomarkers in HCC; nevertheless, we are confident that untangling the mechanisms relevant to TERT
promoter can be a key for developing target therapy for HCC.

DECLARATIONS
Authors’ contributions
Writing the initial manuscript: Ma ZX, Yang CM
Revision of the manuscript: Yang CM, Ma ZX, Li MG
Drafting the outline of the manuscript, critical revision of the manuscript for intellectual content, finalizing
the manuscript, and obtaining the funding: Tu H

Availability of data and materials
Not applicable.

Financial support and sponsorship
This work was supported by grants from the National Natural Science Foundation of China (81572312);
Chinese National Key Project Specialized for Infectious Diseases (2017ZX10201201-008-003); National Key
Research and Development Program of China (2017YFC0908103); and Chinese State Key Laboratory of
Oncogenes and Related Genes (91-14-16, 91-15-06).

Conflicts of interest
All authors declared that there are no conflicts of interest.

Ethical approval and consent to participate
Not applicable.

Consent for publication
Not applicable.

Copyright
© The Author(s) 2019.

REFERENCES
1. Pezzuto F, Buonaguro L, Buonaguro FM, Tornesello ML. Frequency and geographic distribution of TERT promoter mutations in
primary hepatocellular carcinoma. Infect Agent Cancer 2017;12:27.
2. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, et al. Global cancer statistics, 2012. CA Cancer J Clin 2015;65:87-108.
3. Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med
2008;359:378-90.
4. Kudo M. Systemic therapy for hepatocellular carcinoma: latest advances. Cancers (Basel) 2018;10.
5. Ringelhan M, Pfister D, O’Connor T, Pikarsky E, Heikenwalder M. The immunology of hepatocellular carcinoma. Nat Immunol
2018;19:222-32.
6. Zucman-Rossi J, Villanueva A, Nault JC, Llovet JM. Genetic landscape and biomarkers of hepatocellular carcinoma. Gastroenterology
2015;149:1226-39.e4.