PIK3CA and PTEN mutations in adenoid cystic carcinoma of the breast metastatic to kidney.
Adenoid cystic carcinoma (ACC) of the breast rarely metastasizes and has been associated with excellent prognosis. We describe a patient with renal metastasis of primary breast ACC 5 years after the mastectomy. A detailed molecular genetic analysis of the primary and metastatic tumors demonstrated somatic mutations in 2 well-known cancer genes associated with regulation of PI3K/AKT signaling pathway: (1) PIK3CA, which encodes the catalytic alpha subunit of the phosphoinositide-3-kinase, and (2) PTEN, which encodes phosphatase and tensin homolog. The mutation identified in PIK3CA (Ex1+169 A>C) predicts an amino acid change from isoleucine to methionine at codon 31 (I31M) and resides in the p85-binding domain of exon 1. The mutation identified in PTEN (IVS4-3 C>T) resides in intron 4 near the splice acceptor site of exon 5 and was associated with an aberrant PTEN transcript lacking exon 5, which is necessary for protein tyrosine phosphatase function and tumor suppressor properties of PTEN. Increased promoter methylation of PTEN was present in renal metastasis, coinciding with the decrease in the level of normal PTEN transcript. These coexistent mutations/epigenetic inactivations in PI3K/AKT pathway may be responsible for the unusually aggressive course of ACC.
Department of Pathology, Clinical Center of University of Sarajevo, Sarajevo 71000, Bosnia and Herzegovina.
Semir
S
Vranić
Nurija
N
Bilalović
Lisa M J
LM
Lee
Bozo
B
Kruslin
Stan L
SL
Lilleberg
Zoran
Z
Gatalica
D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D002851:Chromatography, High Pressure Liquid; D058534:Class I Phosphatidylinositol 3-Kinases; D003536:Cystadenocarcinoma / Q000235:genetics / Q000556:secondary*; D018076:DNA, Complementary / Q000032:analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000235:genetics / Q000556:secondary*; D009154:Mutation; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D011401:Promoter Regions, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
D014408:Biomarkers, Tumor; D018076:DNA, Complementary; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; D051059:PTEN Phosphohydrolase