Repozitorij Medicinskog fakulteta Sveučilišta u Zagrebu

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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    English abstract

    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
    Divisions: Katedra za patologiju
    Depositing User: Lea Škorić
    Status: Published
    Creators:
    CreatorsEmail
    Vranić, Semir
    Bilalović, Nurija
    Lee, Lisa M.J.
    Krušlin, Božo
    Lilleberg, Stan L.
    Gatalica, Zoran
    Date: September 2007
    Date Deposited: 18 Dec 2007
    Last Modified: 23 Sep 2011 18:10
    Subjects: /
    Related URLs:
      URI: http://medlib.mef.hr/id/eprint/313

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