**5.3 Molecular pathology of ovarian mucinous carcinomas**

OMCs are characterised by *KRAS* and *TP53* mutations (64–66%), *CDKN2A* inactivation (76%) and *HER2/neu* gene amplification (20–26%) [107, 116]. *HER2* gene amplification is almost mutually exclusive to *KRAS* mutations and is found in most of the cases with mutated *TP53* [64%) [116]. OMCs can be developed from benign mucinous tumours through a progression tumour evolution model starting with *KRAS* or *CDKN2A* genomic alterations. Both *KRAS* and *CDKN2A* mutations along with extra genomic copy number aberrations have been found in mucinous borderline tumours and, therefore, are regarded as early molecular events [117, 118]. Chromosomal locus 9p13.3 amplification and *TP53* mutations are identified at the final evolutionary steps of OMCs' progressive carcinogenesis [118]. Other less frequently mutated genes in MOCs are *PIK3CA, PTEN*, *BRAF*, *CTNNB1/APC* (regulators of the β-catenin/Wnt signal transduction pathway), *RNF43* and *ARID1A* (8–12%) [107]. About 34% of

OMCs have neither *KRAS n*or *HER2* gene alterations and are considered to be neoplasms arising from mature cystic teratomas and correlated with an increased risk of recurrence and poor clinical outcome [119]. OMCs with high number of genomic aberrations and mutational burden are associated with high grade and unfavourable prognosis [107]. Targeted therapeutic approaches against *HER2* amplification and/ or *MAPK* pathway mutations might be applied along with other inhibitors, such as HDAC inhibitor for *ARID1A,* for more effective tailored treatment of OMCs [120].
