Frequency of mutations and polymorphisms in borderline ovarian tumors of known cancer genes

Katherine Stemke-Hale, Kristy Shipman, Isidora Kitsou-Mylona, David G. De Castro, Vicky Hird, Robert Brown, James Flanagan, Hani Gabra, Gordon B. Mills, Roshan Agarwal, Mona El-Bahrawy

    Research output: Contribution to journalArticle

    9 Scopus citations

    Abstract

    Borderline ovarian tumors represent an understudied subset of ovarian tumors. Most studies investigating aberrations in borderline tumors have focused on KRAS/BRAF mutations. In this study, we conducted an extensive analysis of mutations and single-nucleotide polymorphisms (SNPs) in borderline ovarian tumors. Using the Sequenom MassArray platform, we investigated 160 mutations/polymorphisms in 33 genes involved in cell signaling, apoptosis, angiogenesis, cell cycle regulation and cellular senescence. Of 52 tumors analyzed, 33 were serous, 18 mucinous and 1 endometrioid. KRAS c.35G>A p.Gly12Asp mutations were detected in eight tumors (six serous and two mucinous), BRAF V600E mutations in two serous tumors, and PIK3CA H1047Y and PIK3CA E542K mutations in a serous and an endometrioid BOT, respectively. CTNNB1 mutation was detected in a serous tumor. Potentially functional polymorphisms were found in vascular endothelial growth factor (VEGF), ABCB1, FGFR2 and PHLPP2. VEGF polymorphisms were the most common and detected at four loci. PHLPP2 polymorphisms were more frequent in mucinous as compared with serous tumors (P=0.04), with allelic imbalance in one case. This study represents the largest and most comprehensive analysis of mutations and functional SNPs in borderline ovarian tumors to date. At least 25% of borderline ovarian tumors harbor somatic mutations associated with potential response to targeted therapeutics.

    Original languageEnglish (US)
    Pages (from-to)544-552
    Number of pages9
    JournalModern Pathology
    Volume26
    Issue number4
    DOIs
    StatePublished - Apr 1 2013

    Keywords

    • borderline
    • ovarian
    • sequenom
    • tumors

    ASJC Scopus subject areas

    • Pathology and Forensic Medicine

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  • Cite this

    Stemke-Hale, K., Shipman, K., Kitsou-Mylona, I., De Castro, D. G., Hird, V., Brown, R., Flanagan, J., Gabra, H., Mills, G. B., Agarwal, R., & El-Bahrawy, M. (2013). Frequency of mutations and polymorphisms in borderline ovarian tumors of known cancer genes. Modern Pathology, 26(4), 544-552. https://doi.org/10.1038/modpathol.2012.194