TY - JOUR
T1 - Frequency of mutations and polymorphisms in borderline ovarian tumors of known cancer genes
AU - Stemke-Hale, Katherine
AU - Shipman, Kristy
AU - Kitsou-Mylona, Isidora
AU - De Castro, David G.
AU - Hird, Vicky
AU - Brown, Robert
AU - Flanagan, James
AU - Gabra, Hani
AU - Mills, Gordon B.
AU - Agarwal, Roshan
AU - El-Bahrawy, Mona
N1 - Funding Information:
The authors are grateful for support from the Imperial College Biomedical Research Centre and Experimental Cancer Medicine Centre grant from Cancer Research UK and the Department of Health. RA is supported by a Clinician Scientist Fellowship from Cancer Research UK. ME is supported by a grant from Ovacome.
PY - 2013/4
Y1 - 2013/4
N2 - 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.
AB - 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.
KW - borderline
KW - ovarian
KW - sequenom
KW - tumors
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U2 - 10.1038/modpathol.2012.194
DO - 10.1038/modpathol.2012.194
M3 - Article
C2 - 23174937
AN - SCOPUS:84876464392
SN - 0893-3952
VL - 26
SP - 544
EP - 552
JO - Modern Pathology
JF - Modern Pathology
IS - 4
ER -