TY - JOUR
T1 - Characterization of fusion genes in common and rare epithelial ovarian cancer histologic subtypes
AU - Earp, Madalene A.
AU - Raghavan, Rama
AU - Li, Qian
AU - Dai, Junqiang
AU - Winham, Stacey J.
AU - Cunningham, Julie M.
AU - Natanzon, Yanina
AU - Kalli, Kimberly R.
AU - Hou, Xiaonan
AU - Weroha, S. John
AU - Haluska, Paul
AU - Lawrenson, Kate
AU - Gayther, Simon A.
AU - Wang, Chen
AU - Goode, Ellen L.
AU - Fridley, Brooke L.
N1 - Funding Information:
The Mayo Clinic Genome Analysis Shared Resource is supported by CA15083 and the Mayo Clinic Center for Individualized Medicine. R01 CA122443, P50 CA136393. K.L. is supported by a K99/R00 Pathway to Independence Award from the NCI (R00CA184415). B.L.F and R.R. were supported by P30 CA168524 and P20 GM103418.
Publisher Copyright:
© Earp et al.
PY - 2017
Y1 - 2017
N2 - Gene fusions play a critical role in some cancers and can serve as important clinical targets. In epithelial ovarian cancer (EOC), the contribution of fusions, especially by histological type, is unclear. We therefore screened for recurrent fusions in a histologically diverse panel of 220 EOCs using RNA sequencing. The Pipeline for RNA-Sequencing Data Analysis (PRADA) was used to identify fusions and allow for comparison with The Cancer Genome Atlas (TCGA) tumors. Associations between fusions and clinical prognosis were evaluated using Cox proportional hazards regression models. Nine recurrent fusions, defined as occurring in two or more tumors, were observed. CRHR1-KANSL1 was the most frequently identified fusion, identified in 6 tumors (2.7% of all tumors). This fusion was not associated with survival; other recurrent fusions were too rare to warrant survival analyses. One recurrent in-frame fusion, UBAP1-TGM7, was unique to clear cell (CC) EOC tumors (in 10%, or 2 of 20 CC tumors). We found some evidence that CC tumors harbor more fusions on average than any other EOC histological type, including high-grade serous (HGS) tumors. CC tumors harbored a mean of 7.4 fusions (standard deviation [sd] = 7.4, N = 20), compared to HGS EOC tumors mean of 2.0 fusions (sd = 3.3, N = 141). Few fusion genes were detected in endometrioid tumors (mean = 0.24, sd = 0.74, N = 55) or mucinous tumors (mean = 0.25, sd = 0.5, N = 4) tumors. To conclude, we identify one fusion at 10% frequency in the CC EOC subtype, but find little evidence for common (> 5% frequency) recurrent fusion genes in EOC overall, or in HGS subtype-specific EOC tumors.
AB - Gene fusions play a critical role in some cancers and can serve as important clinical targets. In epithelial ovarian cancer (EOC), the contribution of fusions, especially by histological type, is unclear. We therefore screened for recurrent fusions in a histologically diverse panel of 220 EOCs using RNA sequencing. The Pipeline for RNA-Sequencing Data Analysis (PRADA) was used to identify fusions and allow for comparison with The Cancer Genome Atlas (TCGA) tumors. Associations between fusions and clinical prognosis were evaluated using Cox proportional hazards regression models. Nine recurrent fusions, defined as occurring in two or more tumors, were observed. CRHR1-KANSL1 was the most frequently identified fusion, identified in 6 tumors (2.7% of all tumors). This fusion was not associated with survival; other recurrent fusions were too rare to warrant survival analyses. One recurrent in-frame fusion, UBAP1-TGM7, was unique to clear cell (CC) EOC tumors (in 10%, or 2 of 20 CC tumors). We found some evidence that CC tumors harbor more fusions on average than any other EOC histological type, including high-grade serous (HGS) tumors. CC tumors harbored a mean of 7.4 fusions (standard deviation [sd] = 7.4, N = 20), compared to HGS EOC tumors mean of 2.0 fusions (sd = 3.3, N = 141). Few fusion genes were detected in endometrioid tumors (mean = 0.24, sd = 0.74, N = 55) or mucinous tumors (mean = 0.25, sd = 0.5, N = 4) tumors. To conclude, we identify one fusion at 10% frequency in the CC EOC subtype, but find little evidence for common (> 5% frequency) recurrent fusion genes in EOC overall, or in HGS subtype-specific EOC tumors.
KW - Fusion gene
KW - Histological subtypes
KW - Ovarian cancer
KW - RNA-sequencing
KW - TCGA
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U2 - 10.18632/oncotarget.16781
DO - 10.18632/oncotarget.16781
M3 - Article
AN - SCOPUS:85024396699
VL - 8
SP - 46891
EP - 46899
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 29
ER -