**3.3 Molecular pathology of ovarian low-grade serous carcinomas**

LGSCs are characterised by genomic stability with low mutation rates, are not associated with *BRCA* germline genomic alterations and display low copy number genetic aberrations, like chromosomal loss of 1p36.33, 9p and homozygous deletions of the *CDKN2A/2B* locus in approximately 86% of LGSCs [71, 72].

*Recent Advances in Classification and Histopathological Diagnosis of Ovarian Epithelial… DOI: http://dx.doi.org/10.5772/intechopen.106545*

The most common molecular alterations found in LGSCs have activated mutations of upstream regulators of MAPK signal transduction pathway like *KRAS* (25–54%), *BRAF* (8–33%), *NRAS* (8–26%) and *ERBB2* (5–6%) [4, 73]. *KRAS* and *BRAF* mutations are early events in LGSCs evolution and can be found in 85% of benign cystadenomas and serous borderline tumours [74]. *KRAS* mutations are associated with aggressive biological behaviour and unfavourable prognosis whereas *BRAF* mutations are found in early clinical stage [75, 76]. Other driver mutations involved in the pathogenetic mechanisms of LGSCs have been observed in *PIK3CA*, *FFAR1*, *MACF1* (11%), *USP9X* (11-27%), *ARID1A* (9%), *NF2* (4%), *DOT1L* (6%), *ASH1L* (4%) and *EIF1AX* (15%) [77]. *USPX9* and *EIF1AX* are downstream effectors of MAPK pathway and linked to the mTOR pathway. Therefore, mTOR inhibitors may be used for targeted therapies in chemoresistant recurrent tumours [78].
