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 Mills, Roshan Agarwal, Mona El-Bahrawy

Research output: Contribution to journalArticle

9 Citations (Scopus)

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
Externally publishedYes

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Neoplasm Genes
Mutation Rate
Mutation
Neoplasms
Vascular Endothelial Growth Factor A
Single Nucleotide Polymorphism
Allelic Imbalance
Cell Aging
Cell Cycle
Apoptosis

Keywords

  • borderline
  • ovarian
  • sequenom
  • tumors

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Stemke-Hale, K., Shipman, K., Kitsou-Mylona, I., De Castro, D. G., Hird, V., Brown, 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

Frequency of mutations and polymorphisms in borderline ovarian tumors of known cancer genes. / Stemke-Hale, Katherine; Shipman, Kristy; Kitsou-Mylona, Isidora; De Castro, David G.; Hird, Vicky; Brown, Robert; Flanagan, James; Gabra, Hani; Mills, Gordon; Agarwal, Roshan; El-Bahrawy, Mona.

In: Modern Pathology, Vol. 26, No. 4, 01.04.2013, p. 544-552.

Research output: Contribution to journalArticle

Stemke-Hale, K, Shipman, K, Kitsou-Mylona, I, De Castro, DG, Hird, V, Brown, R, Flanagan, J, Gabra, H, Mills, G, Agarwal, R & El-Bahrawy, M 2013, 'Frequency of mutations and polymorphisms in borderline ovarian tumors of known cancer genes', Modern Pathology, vol. 26, no. 4, pp. 544-552. https://doi.org/10.1038/modpathol.2012.194
Stemke-Hale K, Shipman K, Kitsou-Mylona I, De Castro DG, Hird V, Brown R et al. Frequency of mutations and polymorphisms in borderline ovarian tumors of known cancer genes. Modern Pathology. 2013 Apr 1;26(4):544-552. https://doi.org/10.1038/modpathol.2012.194
Stemke-Hale, Katherine ; Shipman, Kristy ; Kitsou-Mylona, Isidora ; De Castro, David G. ; Hird, Vicky ; Brown, Robert ; Flanagan, James ; Gabra, Hani ; Mills, Gordon ; Agarwal, Roshan ; El-Bahrawy, Mona. / Frequency of mutations and polymorphisms in borderline ovarian tumors of known cancer genes. In: Modern Pathology. 2013 ; Vol. 26, No. 4. pp. 544-552.
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