Mutations of the PIK3CA gene in diffuse large B cell lymphoma.
The PI3K/AKT pathway might be involved in the development of some certain diffuse large B-cell lymphoma (DLBCL) by as-yet unclear mechanisms. PIK3CA mutations in exons 9 and 20 were investigated in 76 primary human DLBCLs, 3 DLBCL cell lines (LY1, LY8, and LY10), and 9 related samples using polymerase chain reaction-based sequence analysis to assess the possible relevance of PIK3CA mutations in DLBCL to the PI3K/AKT pathway activation. AKT phosphorylation (pAKT) of 3 DLBCL cell lines and 76 primary DLBCL samples was also detected by Western blot and immunohistochemistry. All 3 cell lines showed high levels of pAKT, and 72.4% (55/76) of the DLBCLs expressed pAKT at various levels, indicating the activation of AKT. However, no mutation was found in exons 9 or 20 in PIK3CA in any of the 3 cell lines. Only 1 out of 76 primary DLBCLs (1.32%) harbored an exon 9 mutation, and no exon 20 mutation was detected. The case with mutations contained 3 mutation points. One was c.1634A>C resulting in E545A, which was in a previously reported hotspot. The other 2 were novel c.1658G>C and c.1659delT frameshift mutations. We conclude that the PI3K/AKT pathway is activated in DLBCL and that PIK3CA is rarely mutated in DLBCL, indicating there could be some other PI3K-pathway activation mechanisms operative in DLBCL.
Baohua
Yu
Y
Department of Pathology, Cancer Hospital of Fudan University, Shanghai 200032, People's Republic of China.
Xiaoyan
Zhou
Z
Tiecheng
Zhang
Z
Tao
Qin
Q
Daren
Shi
S
D001483:Base Sequence; D015153:Blotting, Western; D045744:Cell Line, Tumor; D058534:Class I Phosphatidylinositol 3-Kinases; D004252:DNA Mutational Analysis; D006801:Humans; D007150:Immunohistochemistry; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics*; D009154:Mutation; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D010766:Phosphorylation; D016133:Polymerase Chain Reaction; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism
D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; D051057:Proto-Oncogene Proteins c-akt