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Genome-wide association study (GWAS) was also patients, and that losses of 4q, 13q, and 16q are
[31]
applied for SNP analysis of HCC in recent years. In a associated with HBV infection.
GWAS of HCC in Japanese population, one intronic
SNP (rs1012068) in the DEP domain containing Similar to the finding reported by the previous
5 gene was identified to be associated with HCC array CGH based study, a recent whole-genome
risk. In a GWAS of HCC in chronic HBV carriers of sequencing study on HCC showed similar patterns
[21]
Chinese ancestry, one intronic SNP (rs17401966) in of genomic imbalances: The copy number variation
kinesin family member 1B was identified to be highly in HCC genomes is dominated by large-scale
associated with HBV-related HCC. In addition, SNP amplifications and deletions of chromosomal arms
[22]
(rs9679162) in polypeptide N-acetylgalactosaminyl or entire chromosomes including gain at 1q, 5p, 6p,
transferase 14 (GALNT14) have been shown to be 8q, 17q, and 20q; and deletion at Xq or loss at 4p/4q,
associated with chemotherapy response in patients 8p, 13p/13q, 16p/16q, 17p, 21p/21q, and 22q. [2]
with advanced HCC; for advanced HCC patients
treated with FMP (fluorouracil oxantrone cisplatin) Loss of heterozygosity
chemotherapy, GALNT14 genotype (rs9679162) was Loss of heterozygosity (LOH) refers to one of two
an effective predictor of the therapeutic outcome. [23,24] polymorphic alleles on a tumor chromosome.
Zhang et al. identified a high frequency of LOH
[32]
GENOMIC ALTERATION: GENOMIC IMBALANCES 4q (48.1%) in HCC, in which the caspase-6 and ras-
related C3 botulinum toxin substrate 1 pseudogene
Copy number variation-genomic gain or loss 5 in the region 4q24-26 may be related with tumor
Chromosomal abnormalities in HCC have been well growth. Additionally, inhibitor of growth family,
reported, and comparative genomic hybridization member 2 (ING2) in the region 4q34.3-4q35 was
(CGH) has revealed a consistent pattern of genomic found to be down-regulated frequently in HCC, and
gains and losses involved in the development and its gene expression was also significantly decreased,
progression of HCC. The most prominent changes suggesting that ING2 might be a tumor-specific
are partial or entire gains of chromosome arms 1q, glycoprotein of HCC. In a variety of human tumors,
[32]
8q, and 2q; and losses of 1, 4q, 8p, 13q, 16q, and the most common chromosomal changes were 8p
17p. In one meta-analysis, using conventional CGH allelic loss, suggesting that there might be one or
analysis with low resolution (approximately 2 Mb) several tumor suppressor genes on the short arm
from several studies, it was revealed that the most of chromosome 8. LOH was frequently observed
prominent changes were gains of 1q (57.1%), 8q on chromosomes 8p22-23, but the gene closely
(46.6%), 6p (23.3%), and 17q (22.2%); and losses of related with HCC was still unknown. However, Peng
8p (38%), 16q (35.9%), 4q (34.3%), 17p (32.1%), and et al. identified that LOH of zinc finger, DHHC-
[33]
[25]
13q (26.2%). Using array CGH analysis from four type containing 2 (in 8p22-23 was associated with
studies, it was revealed that loci with genomic gains early metastatic recurrence of HCC after liver
with a prevalence of more than 25% included 1q, 6p, transplantation.
8q, 17q, 20p, 5p15.33, and 9q34.2-34.3; and loci
with genomic losses with prevalence of more than Gene amplification and deletion
25% comprised 4q, 6q, 8p, 9p, 13q, 14q, 16q, and Gene amplification in certain regions of chromosomes
17p; and were associated with 31 classical molecular plays a crucial role in the development and progression
pathways, particularly the antivirus immunological of human malignancies. Recently, researchers found
[25]
pathway. A series of tumor suppressor genes amplification of the ecotropic viral integration site
have been identified in these regions, such as PR 1 (EVI1) gene at the chromosomal region 3q26 in
domain containing 5 (PRDM5, 4q26), TP53 (17p13.1), the HCC cell line JHH-1. A copy number gain of
[34]
retinoblastoma 1 (RB1, 13q14), and cadherin 1, type EVI1 was observed in 36% (24/66) of primary HCC
1 (CDH1, 16q22.1). [26-28] Some clinicopathological tumors. EVI1 antagonizes TGF-β-mediated growth
associations have been noted with specific inhibition in HCC cells, suggesting the EVI1 may be
abnormalities: Losses of 4q, 13q, and 16q are a potential molecular target for the development
associated with HBV infection, loss of 4q has been of novel therapies to treat HCC. In another study,
[34]
[25]
associated with elevated α-fetoprotein levels, TP53 granulin-epithelin precursor, a secretory growth
mutations, tumor size, and vascular invasion factor, was identified with gene amplification in 20%
[29]
[30]
while 9p and 6q losses have been reported to be of HCC cases, and this amplification was correlated
independent predictors of poor outcome of HCC with enhanced expression levels in the same HCC
Hepatoma Research | Volume 2| Issue 2 | February 29, 2016 33