[Screening for mutations in the hotspot mutation regions of PIK3CA gene in nasopharyngeal carcinoma].

Background & Objective: Recent studies showed high frequency of phosphatidylinositol 3-kinase catalytic alpha polypeptide (PIK3CA) mutations in various human cancers; notably, these mutations frequently locate in the hotspot mutation regions of PIK3CA exon 9 and exon 20 with functional significance in tumorigenesis, invasion, and anti-apoptosis. This study was to screen for mutations in the hotspot mutation regions of PIK3CA in nasopharyngeal carcinoma (NPC), and explore the correlation of PIK3CA mutations to tumorigenesis of NPC.

Methods: PIK3CA exon 9 and exon 20 in 46 specimens of sporadic primary NPC tissues were screened by polymerase chain reaction (PCR)-clone sequencing; those in 46 samples of matched NPC peripheral blood and 3 NPC cell lines CNE1, CNE2, and SUNE1 were directly sequenced.

Results: Among the 46 specimens of NPC, 2 (4.3%) had point mutation in PIK3CA exon 9 [T1563G (521Asn-->Lys) and A1646G (549Asp-->Gly)], 18 had multiple mutations in PIK3CA exon 9 (A1634C-G1658C-del 1659T), which might be the homologous sequence of Cat Eye Syndrome region on 22q11.2; none had mutation in PIK3CA exon 20. Moreover, no mutation was detected in PIK3CA exon 9 and exon 20 in the 46 matched NPC peripheral blood samples and CNE1, CNE2, and SUNE1 cells.

Conclusions: PIK3CA exon 9 and exon 20 rarely mutate in NPC. Clone sequencing is more sensitive than direct sequencing in screening for somatic mutation. A1634C-G1658C-del 1659T mutations in PIK3CA exon 9, detected by clone sequencing, are supposed to be the homologous sequence of Cat Eye Syndrome region on 22q11.2 instead of mutations in PIK3CA.