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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Curr+Genomics
2014 ; 15
(6
): 469-80
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Somatic mutations, viral integration and epigenetic modification in the evolution
of hepatitis B virus-induced hepatocellular carcinoma
#MMPMID25646075
Ji X
; Zhang Q
; Du Y
; Liu W
; Li Z
; Hou X
; Cao G
Curr Genomics
2014[Dec]; 15
(6
): 469-80
PMID25646075
show ga
Liver cancer in men is the second leading cause of cancer death and
hepatocellular carcinoma (HCC) accounts for 70%-85% of the total liver cancer
worldwide. Chronic infection with hepatitis B virus (HBV) is the major cause of
HCC. Chronic, intermittently active inflammation provides "fertile field" for
"mutation, selection, and adaptation" of HBV and the infected hepatocytes, a
long-term evolutionary process during HBV-induced carcinogenesis. HBV mutations,
which are positively selected by insufficient immunity, can promote and predict
the occurrence of HCC. Recently, advanced sequencing technologies including whole
genome sequencing, exome sequencing, and RNA sequencing provide opportunities to
better under-stand the insight of how somatic mutations, structure variations,
HBV integrations, and epigenetic modifications contribute to HCC development.
Genomic variations of HCC caused by various etiological factors may be different,
but the common driver mutations are important to elucidate the HCC evolutionary
process. Genome-wide analyses of HBV integrations are helpful in clarifying the
targeted genes of HBV in carcinogenesis and disease progression. RNA sequencing
can identify key molecules whose expressions are epigenetically modified during
HCC evolution. In this review, we summarized the current findings of next
generation sequencings for HBV-HCC and proposed a theory framework of Cancer
Evolution and Development based on the current knowledge of HBV-induced HCC to
characterize and interpret evolutionary mechanisms of HCC and possible other
cancers. Understanding the key viral and genomic variations involved in HCC
evolution is essential for generating effective diagnostic, prognostic, and
predictive biomarkers as well as therapeutic targets for the interventions of
HBV-HCC.