Yonsei Med J.  2013 Jul;54(4):883-887. 10.3349/ymj.2013.54.4.883.

PIK3CA Mutations in Hepatocellular Carcinoma in Korea

• Kim H
• Park CK
• Lee SJ
• Rha SY
• Park KH
• Lim HY

• KMID: 2158221
• DOI: http://doi.org/10.3349/ymj.2013.54.4.883

Abstract

PURPOSE
Phosphatidylinositol 3-kinases/AKT pathway plays a pivotal role in hepatocellular carcinoma (HCC). Mutant PIK3CA, encoding the p110a catalytic subunit, stimulates the AKT pathway and promotes cell growth in various cancers. PIK3CA mutation rate has been usually reported as low frequency (<5%) in HCC except one report from Korea with 35.6%. Therefore, we investigated the frequency of PIK3CA mutations in Korean HCC patients.
MATERIALS AND METHODS
We sequenced exons1, 3, 4, 6, 7, 8, 9, 19 and 20 of PIK3CA in 268 HCC tumor tissue samples by Sanger method and pyrosequencing assay.
RESULTS
In this study, the mutations were not detected in exons3, 6, 8, and 19, and detected 1 at unknown SNP in exon1 and exon4, 2 at unknown SNP in exon7, 2 at unknown SNP in exon20. However, 1 at unknown SNP, 1 at G1635T and surprisingly all samples at A1634Cin exon9 were detected by Sanger method. Additional experiments with normal tissue, cloning experiments and a pyrosequencing assay revealed that the double peak at A1634C of exon9 is a pseudogene, not true mutation. The mutations found in this study were all different and small numbers, therefore, we cannot conclude specific relationship between clinical characteristics of HCC and mutation of PIK3CA.
CONCLUSION
Our study suggests that the rate of PIK3CA mutation in the Korea population is in fact similar to the rates seen elsewhere in the world.

Keyword

PIK3CA; mutation; hepatocellular carcinoma

MeSH Terms

Adolescent
Adult
Aged
Asian Continental Ancestry Group/genetics
Carcinoma, Hepatocellular/*genetics
Exons
Female
Humans
Liver Neoplasms/*genetics
Male
Middle Aged
*Mutation
Mutation Rate
Phosphatidylinositol 3-Kinases/*genetics
Polymorphism, Single Nucleotide
Republic of Korea
Young Adult
Phosphatidylinositol 3-Kinases

Figure

• 

  Fig. 1 Sequencing results of PIK3CA gene. (A) Electropherograms show the SNP in each exon in 268 HCC samples. (B) Electropherograms show the nucleotide sequences of the genomic DNA from red box, indicating double peak at 1634 of exon9 in 268 HCC samples. HCC, hepatocellular carcinoma.

• 

  Fig. 2 Results of codon 545 by pyrosequencing. Pyrosequencing results show the specificity of PIK3CA amplification for codon 545. Pyrogram for amplification of a sample using PIK3CA condon 545 is GAG, and the pseudogene was not amplified.

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