Frequency and geographic distribution of TERT promoter mutations in primary hepatocellular carcinoma

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4 Citations (Scopus)

Abstract

Primary hepatocellular carcinoma (HCC) mainly develops in subjects chronically infected with hepatitis B (HBV) and C (HCV) viruses through a multistep process characterized by the accumulation of genetic alterations in the human genome. Nucleotide changes in coding regions (i.e. TP53, CTNNB1, ARID1A and ARID2) as well as in non-coding regions (i.e. TERT promoter) are considered cancer drivers for HCC development with variable frequencies in different geographic regions depending on the etiology and environmental factors. Recurrent hot spot mutations in TERT promoter (G > A at-124 bp; G > A at −146 bp), have shown to be common events in many tumor types including HCC and to up regulate the expression of telomerases. We performed a comprehensive review of the literature evaluating the differential distribution of TERT promoter mutations in 1939 primary HCC from four continents. Mutation rates were found higher in Europe (56.6%) and Africa (53.3%) than America (40%) and Asia (42.5%). In addition, HCV-related HCC were more frequently mutated (44.8% in US and 69.7% in Asia) than HBV-related HCC (21.4% in US and 45.5% in Africa). HCC cases associated to factors other than hepatitis viruses are also frequently mutated in TERT promoter (43.6%, 52.6% and 57.7% in USA, Asia and Europe, respectively). These results support a major role for telomere elongation in HCV-related and non-viral related hepatic carcinogenesis and suggest that TERT promoter mutations could represent a candidate biomarker for the early detection of liver cancer in subjects with HCV infection or with metabolic liver diseases.

Original languageEnglish
Pages (from-to)1-9
Number of pages9
JournalInfectious Agents and Cancer
Volume12
Issue number1
DOIs
Publication statusPublished - May 19 2017

Fingerprint

Hepatocellular Carcinoma
Mutation
Hepatitis Viruses
Telomerase
Metabolic Diseases
Telomere
Human Genome
Mutation Rate
Liver Neoplasms
Hepatitis C
Hepatitis B
Early Detection of Cancer
Liver Diseases
Neoplasms
Carcinogenesis
Up-Regulation
Nucleotides
Biomarkers
Viruses
Liver

Keywords

  • Hepatitis B virus
  • Hepatitis C virus
  • Hepatocellular carcinoma
  • Telomerase
  • TERT promoter mutations

ASJC Scopus subject areas

  • Epidemiology
  • Oncology
  • Cancer Research
  • Infectious Diseases

Cite this

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title = "Frequency and geographic distribution of TERT promoter mutations in primary hepatocellular carcinoma",
abstract = "Primary hepatocellular carcinoma (HCC) mainly develops in subjects chronically infected with hepatitis B (HBV) and C (HCV) viruses through a multistep process characterized by the accumulation of genetic alterations in the human genome. Nucleotide changes in coding regions (i.e. TP53, CTNNB1, ARID1A and ARID2) as well as in non-coding regions (i.e. TERT promoter) are considered cancer drivers for HCC development with variable frequencies in different geographic regions depending on the etiology and environmental factors. Recurrent hot spot mutations in TERT promoter (G > A at-124 bp; G > A at −146 bp), have shown to be common events in many tumor types including HCC and to up regulate the expression of telomerases. We performed a comprehensive review of the literature evaluating the differential distribution of TERT promoter mutations in 1939 primary HCC from four continents. Mutation rates were found higher in Europe (56.6{\%}) and Africa (53.3{\%}) than America (40{\%}) and Asia (42.5{\%}). In addition, HCV-related HCC were more frequently mutated (44.8{\%} in US and 69.7{\%} in Asia) than HBV-related HCC (21.4{\%} in US and 45.5{\%} in Africa). HCC cases associated to factors other than hepatitis viruses are also frequently mutated in TERT promoter (43.6{\%}, 52.6{\%} and 57.7{\%} in USA, Asia and Europe, respectively). These results support a major role for telomere elongation in HCV-related and non-viral related hepatic carcinogenesis and suggest that TERT promoter mutations could represent a candidate biomarker for the early detection of liver cancer in subjects with HCV infection or with metabolic liver diseases.",
keywords = "Hepatitis B virus, Hepatitis C virus, Hepatocellular carcinoma, Telomerase, TERT promoter mutations",
author = "Francesca Pezzuto and Luigi Buonaguro and Buonaguro, {Franco M.} and Tornesello, {Maria Lina}",
year = "2017",
month = "5",
day = "19",
doi = "10.1186/s13027-017-0138-5",
language = "English",
volume = "12",
pages = "1--9",
journal = "Infectious Agents and Cancer",
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publisher = "BioMed Central",
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TY - JOUR

T1 - Frequency and geographic distribution of TERT promoter mutations in primary hepatocellular carcinoma

AU - Pezzuto, Francesca

AU - Buonaguro, Luigi

AU - Buonaguro, Franco M.

AU - Tornesello, Maria Lina

PY - 2017/5/19

Y1 - 2017/5/19

N2 - Primary hepatocellular carcinoma (HCC) mainly develops in subjects chronically infected with hepatitis B (HBV) and C (HCV) viruses through a multistep process characterized by the accumulation of genetic alterations in the human genome. Nucleotide changes in coding regions (i.e. TP53, CTNNB1, ARID1A and ARID2) as well as in non-coding regions (i.e. TERT promoter) are considered cancer drivers for HCC development with variable frequencies in different geographic regions depending on the etiology and environmental factors. Recurrent hot spot mutations in TERT promoter (G > A at-124 bp; G > A at −146 bp), have shown to be common events in many tumor types including HCC and to up regulate the expression of telomerases. We performed a comprehensive review of the literature evaluating the differential distribution of TERT promoter mutations in 1939 primary HCC from four continents. Mutation rates were found higher in Europe (56.6%) and Africa (53.3%) than America (40%) and Asia (42.5%). In addition, HCV-related HCC were more frequently mutated (44.8% in US and 69.7% in Asia) than HBV-related HCC (21.4% in US and 45.5% in Africa). HCC cases associated to factors other than hepatitis viruses are also frequently mutated in TERT promoter (43.6%, 52.6% and 57.7% in USA, Asia and Europe, respectively). These results support a major role for telomere elongation in HCV-related and non-viral related hepatic carcinogenesis and suggest that TERT promoter mutations could represent a candidate biomarker for the early detection of liver cancer in subjects with HCV infection or with metabolic liver diseases.

AB - Primary hepatocellular carcinoma (HCC) mainly develops in subjects chronically infected with hepatitis B (HBV) and C (HCV) viruses through a multistep process characterized by the accumulation of genetic alterations in the human genome. Nucleotide changes in coding regions (i.e. TP53, CTNNB1, ARID1A and ARID2) as well as in non-coding regions (i.e. TERT promoter) are considered cancer drivers for HCC development with variable frequencies in different geographic regions depending on the etiology and environmental factors. Recurrent hot spot mutations in TERT promoter (G > A at-124 bp; G > A at −146 bp), have shown to be common events in many tumor types including HCC and to up regulate the expression of telomerases. We performed a comprehensive review of the literature evaluating the differential distribution of TERT promoter mutations in 1939 primary HCC from four continents. Mutation rates were found higher in Europe (56.6%) and Africa (53.3%) than America (40%) and Asia (42.5%). In addition, HCV-related HCC were more frequently mutated (44.8% in US and 69.7% in Asia) than HBV-related HCC (21.4% in US and 45.5% in Africa). HCC cases associated to factors other than hepatitis viruses are also frequently mutated in TERT promoter (43.6%, 52.6% and 57.7% in USA, Asia and Europe, respectively). These results support a major role for telomere elongation in HCV-related and non-viral related hepatic carcinogenesis and suggest that TERT promoter mutations could represent a candidate biomarker for the early detection of liver cancer in subjects with HCV infection or with metabolic liver diseases.

KW - Hepatitis B virus

KW - Hepatitis C virus

KW - Hepatocellular carcinoma

KW - Telomerase

KW - TERT promoter mutations

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U2 - 10.1186/s13027-017-0138-5

DO - 10.1186/s13027-017-0138-5

M3 - Review article

VL - 12

SP - 1

EP - 9

JO - Infectious Agents and Cancer

JF - Infectious Agents and Cancer

SN - 1750-9378

IS - 1

ER -