Somatic genomic and transcriptomic characterization of primary ovarian serous borderline tumors and low-grade serous carcinomas.

Low-grade serous carcinomas (LGSC) probably develop from serous borderline tumors (SBT), where the micropapillary type (mSBT) has the highest risk of progression. The sensitivity of LGSC to standard chemotherapy is limited, so alternative therapeutic approaches are needed, including targeted treatment. However, current knowledge about molecular landscape of LGSC and mSBT is limited. A sample set of 137 pathologically well-defined cases of 40 mSBT and 97 LGSC was analysed using capture DNA NGS (727 genes) and RNA-Seq (147 genes) to show the landscape of somatic mutations, gene fusions, and the expression pattern, as well as their prognostic and predictive relevance. Class 4/5 mutations in the main driver genes (KRAS, BRAF, NRAS, ERBB2; USP9X) have been detected in 48% (14/29) mSBT and 63% (47/75) LGSC. The USP9X mutation was detected only in 17% LGSC. RNA-Seq revealed gene fusions in 6/64 (9%) LGSC and 2/33 (9%) mSBT, and a heterogeneous expression profile across mSBT and LGSC. No association of any molecular characteristics with better survival was found. This study presents and compares the somatic genomic and transcriptomic profile of 35 mSBT and 85 LGSC which is being described for the first time. Candidate oncogenic gene fusions involving BRAF, FGFR2 or NF1 as a fusion partner were identified. Molecular testing of LGSC may be used in clinical practice to reveal therapeutically significant targets.