scholarly journals Loss of heterozygosity on chromosome 10q23 and mutation of the phosphatase and tensin homolog deleted from chromosome 10 tumor suppressor gene in Korean hepatocellular carcinoma patients

2007 ◽  
Author(s):  
Jei-Jun Bae ◽  
Jin-Woo Rho ◽  
Tae-Jin Lee ◽  
Sung-Su Yun ◽  
Hong-Jin Kim ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Loss Of Heterozygosity ◽  
Suppressor Gene ◽  
Chromosome 10 ◽  
Phosphatase And Tensin Homolog ◽  
Tensin Homolog

scholarly journals Parkin as a tumor suppressor gene for hepatocellular carcinoma

Oncogene ◽  
2008 ◽  
Vol 27 (46) ◽  
pp. 6002-6011 ◽  
Author(s):  
M Fujiwara ◽  
H Marusawa ◽  
H-Q Wang ◽  
A Iwai ◽  
K Ikeuchi ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Suppressor Gene

P53 tumor suppressor gene mutations in hepatocellular carcinoma patients in India

Cancer ◽  
2000 ◽  
Vol 88 (7) ◽  
pp. 1565-1573 ◽  
Author(s):  
Sanjay Katiyar ◽  
Bipin C. Dash ◽  
Varsha Thakur ◽  
Raj C. Guptan ◽  
Shiv K. Sarin ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Gene Mutations ◽  
Suppressor Gene ◽  
P53 Tumor Suppressor ◽  
P53 Tumor Suppressor Gene

Translational significance of a newly identified hepatocellular carcinoma tumor suppressor gene on chromosome 8p.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15097-e15097
Author(s):  
Han Chong Toh ◽  
Francis Enane ◽  
Marissa Teo ◽  
Hideki Makishima ◽  
JoAnna Ng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Snp Array ◽  
Uniparental Disomy ◽  
Biological Significance ◽  
Suppressor Gene ◽  
Cell Cycle Exit ◽  
Malignant Liver

e15097 Background: After deletion of 17p that removes the tumor suppressor gene (TSG) TP53, deletion of 8p is the next most common chromosome abnormality in hepatocellular carcinoma (HCC). However, 8p TSG are insufficiently defined. Methods: Integrated genomic analysis of HCC and non-malignant liver obtained at therapeutic segmentectomy from the same patients. Results: A minimally deleted region on 8p was identified by SNP array. This incorporated GATA4. Therefore, GATA4 was Sanger sequenced in paired HCC/non-malignant liver: recurrent somatic non-synonymous missense mutations were identified in exon 4 (V267M n=5) or exon 6 (S357T n=6, R362N n=2, T366R n=2). Biallelic abnormalities were deletion and mutation (n=6) or mutation and uniparental disomy (n=4), with mutation or deletion of at least one GATA4 allele in 29/47 (62%) of HCC cases. The other GATA4 exons were mutation free. Although missense mutation is not intrinsically expected to decrease GATA4 expression, GATA4 mRNA was significantly decreased in cases with mutation as well as deletion (p<0.01) compared to non-malignant liver or wild-type GATA4 HCC. GATA4 drives liver differentiation, and the biological significance of GATA4 deficiency was demonstrated by significant enrichment (49%) for liver differentiation genes (p<1.2exp-124, Benjamini corrected) amongst genes with decreased expression in HCC compared to non-malignant liver. From an oncogenesis perspective, the most important of these hepatocyte genes (e.g., HNF4A, CEBPD) antagonize MYC to terminate proliferation: GATA4 introduction (expression vector) into HCC cells containing mutated or deleted GATA4 (HepG2 and PLC respectively) restored HNF4A and CEBPD expression, suppressed MYC protein, upregulated p27/CDKN1B that mediates cell cycle exit by maturation and significantly decreased HCC proliferation without apoptosis. In objectively quantified immunohistochemical analyses (ImageIQ), HCC cases with GATA4 mutation/deletion had significantly increased MYC protein (p<0.05). Conclusions: 8p deletion/GATA4 mutation in HCC suppresses cell cycle exit by maturation, thus complementing 17p deletion that suppresses cell cycle exit by apoptosis.

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