By ecancer reporter Jo Armstrong

Presentation: Molecular subtypes of ovarian cancer: insights into the drivers of high-grade ovarian serous and clear cell tumours - DDL Bowtell

Recent pathological and molecular studies have forced a very significant re-evaluation of the conventional classification of ovarian cancers, which is now recognised as a series of molecularly distinct diseases that individually bear more resemblance to certain non-ovarian cancers than they do to each other. Ovarian cancer really represents a spectrum of distinct diseases that share an anatomical location. There is now an increasing understanding of the molecular differences between and within different ovarian cancer histotypes, with four very distinct high grade ovarian serous subtypes identified: C1, C2, C4 and C5. These account for about two thirds of ovarian cancer deaths. These subtypes are associated with different survival outcomes, with C2 the most favourable, followed by C4, C5 and lastly C1, with the least favourable outcome. Interestingly, immune expression for these subtypes appears to be inversely related. A complex pathway of tumour regulation involving a number of transcription factors has been elucidated for the C5 subtype, which represented around 10-15% of high grade ovarian tumours. The pathway involves the N-Myc gene, which is over-expressed in this tumour subtype. It regulates Lin28B, which in turn regulates the LET7 microRNA family that control HMGA2. HMGA2 is the highest expressed gene in C5, and has also been found to be expressed in a wide range of solid tumour cells. In clear cell tumours, which are refractory to platinum-based therapy, a distinct pattern of gene expression resulting in the deregulation of receptor tyrosine kinases and cytokine pathways has been observed. This deregulation results in the upregulation of the IL6/STAT3/HIF pathway.