PIK3CA and PTEN mutations in adenoid cystic carcinoma of the breast metastatic to kidney

Vranić, Semir and Bilalović, Nurija and Lee, Lisa M.J. and Krušlin, Božo and Lilleberg, Stan L. and Gatalica, Zoran (2007) PIK3CA and PTEN mutations in adenoid cystic carcinoma of the breast metastatic to kidney. Human Pathology, 38 (9). pp. 1425-1431. ISSN 0046-8177

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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.

Item Type: Article
MeSH: 1-Phosphatidylinositol 3-Kinase - genetics ; Breast Neoplasms - genetics - pathology ; Cystadenocarcinoma - genetics - secondary ; Kidney Neoplasms - genetics - secondary ; Mutation ; PTEN Phosphohydrolase - genetics ; Tumor Markers, Biological - genetics ; Aged ; Chromatography, High Pressure Liquid ; DNA, Complementary - analysis ; Female ; Humans ; Immunohistochemistry ; Promoter Regions (Genetics) ; Reverse Transcriptase Polymerase Chain Reaction ; Sequence Analysis, DNA
Departments: Katedra za patologiju
Depositing User: Lea Škorić
Status: Published
Bilalović, NurijaUNSPECIFIED
Lilleberg, Stan L.UNSPECIFIED
Gatalica, ZoranUNSPECIFIED
Date: September 2007
Date Deposited: 18 Dec 2007
Last Modified: 23 Sep 2011 16:10
Subjects: /
Related URLs:
    URI: http://medlib.mef.hr/id/eprint/313

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