Mutation of PIK3CA: possible risk factor for cervical carcinogenesis in older women.
PIK3CA encodes the p110alpha catalytic subunit of PI 3-kinase, which regulates signaling pathways important for neoplasia, cell proliferation and apoptosis. Somatic mutations in this gene have been detected in several solid human tumors. We investigated these mutations in cervical carcinoma and its precursors, and their association with HPV infection and patient clinical data. The mutations were analyzed using post-PCR direct genomic DNA sequencing. Samples included 9 cervical cancer cell lines, 184 invasive cervical carcinomas, and 30 cervical neoplasias. Missense mutations of PIK3CA were identified in 15/184 (8.15%) invasive cervical carcinomas. One novel mutation G1638C (Q546H) was found. Three mutations were identified in the cervical cancer lines. No mutations were found in the precursors. The difference in mutation frequency between invasive and pre-invasive lesions was not significant (p=0.1372). In relation to age and HPV, the mutation rate was significantly higher in patients>or=60 years (p=0.001), while the rate of HPV infection was higher in patients<or=60 years (p=0.025). No significant correlation with other clinicopathological data was found. The results suggest that PIK3CA mutations are a late event and uncommon in the progression of malignant tumors, but it appears that they facilitate carcinogenesis in older women.
Cui
Baoxia
B
Department of Molecular Medicine and Surgery, Karolinska University Hospital Solna, Karolinska Institutet, Stockholm, Sweden. baoxiacui@hotmail.com
Zheng
Biying
B
Zhang
Xi
X
Stendahl
Ulf
U
Andersson
Sonia
S
Wallin
Keng-Ling
KL
D000368:Aged; D045744:Cell Line, Tumor; D058534:Class I Phosphatidylinositol 3-Kinases; D017931:DNA Primers; D005260:Female; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D020125:Mutation, Missense; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D027383:Papillomaviridae / Q000302:isolation & purification; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D016133:Polymerase Chain Reaction; D016019:Survival Analysis; D002583:Uterine Cervical Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000401:mortality / Q000821:virology
D017931:DNA Primers; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human