OBJECTIVES:
The
phosphatidylinositol 3-kinase/AKT axis is an important
cell-signaling pathway that mediates
cell proliferation and
survival, two
biological processes that regulate malignant
cell growth. The
phosphatidylinositol 3-kinase CA
gene encodes the p110α subunit of the
phosphatidylinositol 3-kinase protein. There are
phosphatidylinositol 3-kinase CA
mutations in several types of
human tumors, and they are frequently observed in
breast cancer. However, these
mutations have not been investigated in Brazilian
breast cancer patients.
METHODS:
PCR-
SSCP and direct
DNA sequencing were performed to identify
phosphatidylinositol 3-kinaseCA
exon 9 and
exon 20
mutations in 86
patients with sporadic
breast cancer. The relationships between PIK3CA
mutations and
patient clinicopathological characteristics and
survival were analyzed. The presence of the TP53
mutation was also examined.
RESULTS:
Twenty-three (27%) of the 86 primary
breast tumors contained PIK3CA
mutations. In
exons 9 and 20, we identified the hotspot
mutations E542K, E545K, and H1047R, and we identified two new
missense mutations (I1022V and L1028S) and one nonsense (R992X)
mutation.
Phosphatidylinositol 3-kinase CA
exon 20
mutations were associated with poor overall
survival and
TP53 gene mutations.
CONCLUSIONS:
Phosphatidylinositol 3-kinase CA
mutations are common in
tumors in Brazilian
breast cancer patients, and
phosphatidylinositol 3-kinase CA and TP53
mutations are not mutually exclusive.
Phosphatidylinositol 3-kinase CA
exon 20
mutations are associated with poor
survival, and they may be useful
biomarkers for identifying
breast cancer patients with aggressive
tumors and for predicting the response to
treatment with PI3K pathway inhibitors.