PIK3CA hypomethylation plays a key role in activation of the PI3K/AKT pathway in esophageal cancer in Chinese patients.
OBJECTIVE
To investigate the role of PIK3CA oncogene in tumorigenesis and development of esophageal cancer in Chinese patients at the levels of genetic mutation and epigenetics.


METHODS
Seventy six esophageal tumor samples and corresponding adjacent normal tissues were collected, and the genomic DNA was extracted. Mutations in the 9th and 20th exons of PIK3CA gene were detected using conventional sequencing. PIK3CA methylation rates in two selected CpG islands (CpG island 1 and 2) were detected using sub-bisulfate modified sequencing. P110α and pAKT expression levels were detected with Western blotting.


RESULTS
In PIK3CA gene of the tumor tissues, G1633C (E545Q) mutation was detected in the 9th exon with a rate of 3.95% (3/76), whereas mutation was not found in the 20th exon. Nor mutation did occur in PIK3CA gene of the adjacent normal tissues. The methylation rate of the CpG island 1 had no significant difference between the tumor and adjacent tissues (0.77%±0.009% vs 0.89%±0.008%), but the methylation rate of the CpG island 2 in the esophageal tumors was significantly lower than that in the adjacent tissues (6.00%±2.80% vs 10.45%±5.51%). Furthermore, the rate of methylation of the CpG island 2 in TNM stage III and IV esophageal cancer (3.84%±2.08%) was significantly lower than in stage I (8.52%±2.55%) and stage II (6.42%±2.36%). PIK3CA gene hypomethylation in esophageal cancer was significantly correlated with high expression of p110α.


CONCLUSIONS
PIK3CA gene hypomethylation plays a key role in the tumorigenesis and development of esophageal cancer in Chinese patients, while the mutations of PIK3CA gene have little effect on the development of esophageal cancer.
Department of Chest Surgery, First Affiliated Hospital of Soochow University, Suzhou 215006, China.
Wei-feng
WF
Wang
Yan
Y
Xie
Zhi-hua
ZH
Zhou
Zheng-hong
ZH
Qin
Jun-chao
JC
Wu
Jing-kang
JK
He
D000328:Adult; D001483:Base Sequence; D015153:Blotting, Western; D002681:China; D058534:Class I Phosphatidylinositol 3-Kinases; D017931:DNA Primers; D004789:Enzyme Activation; D004938:Esophageal Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008745:Methylation; D008875:Middle Aged; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*
D017931:DNA Primers; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; D051057:Proto-Oncogene Proteins c-akt