Mutation and genomic amplification of the PIK3CA proto-oncogene in pituitary adenomas.
The tumorigenesis of pituitary adenomas is poorly understood. Mutations of the PIK3CA proto-oncogene, which encodes the p110-α catalytic subunit of PI3K, have been reported in various types of human cancers regarding the role of the gene in cell proliferation and survival through activation of the PI3K/Akt signaling pathway. Only one Chinese study described somatic mutations and amplification of the PIK3CA gene in a large series of pituitary adenomas. The aim of the present study was to determine genetic alterations of PIK3CA in a second series that consisted of 33 pituitary adenomas of different subtypes diagnosed by immunohistochemistry: 6 adrenocorticotropic hormone-secreting microadenomas, 5 growth hormone-secreting macroadenomas, 7 prolactin-secreting macroadenomas, and 15 nonfunctioning macroadenomas. Direct sequencing of exons 9 and 20 assessed by qPCR was employed to investigate the presence of mutations and genomic amplification defined as a copy number ≥4. Previously identified PIK3CA mutations (exon 20) were detected in four cases (12.1%). Interestingly, the Chinese study reported mutations only in invasive tumors, while we found a PIK3CA mutation in one noninvasive corticotroph microadenoma. PIK3CA amplification was observed in 21.2% (7/33) of the cases. This study demonstrates the presence of somatic mutations and amplifications of the PIK3CA gene in a second series of pituitary adenomas, corroborating the previously described involvement of the PI3K/Akt signaling pathway in the tumorigenic process of this gland.
Laboratório de Endocrinologia Celular e Molecular (LIM-25), Universidade de São Paulo, São Paulo, SP, Brasil.
C B
CB
Murat
P B S
PB
Braga
M A H Z
MA
Fortes
M D
MD
Bronstein
M L C
ML
Corrêa-Giannella
R R
RR
Giorgi
D000236:Adenoma / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D058534:Class I Phosphatidylinositol 3-Kinases; D005260:Female; D005784:Gene Amplification / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D010911:Pituitary Neoplasms / Q000235:genetics*; D000090063:Proto-Oncogene Mas; D015398:Signal Transduction; D055815:Young Adult
D058534:Class I Phosphatidylinositol 3-Kinases; D019869:Phosphatidylinositol 3-Kinases; D000090063:Proto-Oncogene Mas; C000715470:MAS1 protein, human; C484760:PIK3CA protein, human