While epigenetic variation underlies the origin of many cancers, underlying epigenetic similarities can reveal cancer’s tissue of origin. High-grade serous ovarian cancer (HGSC) is the most common and serious type of epithelial ovarian cancer. However, there are two competing hypotheses about which tissue HGSC arises from. Ovarian surface epithelia (OSE) has been implicated, but the fallopian tube fimbriae epithelia (FTE) has more recently arisen as a new contender.
In order to settle this original mystery, a study led by the lab of Adam Karpf at the University of Nebraska Medical Center has examined the methylomes of HGSC alongside patient matched normal OSE and FTE.
Here’s what they found by using the Illumina 450K beadchip array and Agilent SureSelect Methylome bisulfite sequencing on their samples to identify differentially methylated CpGs (DMC) and larger differentially methylated regions (DMRs), respectively:
- There are 19,102 DMCs and 741 DMRs when comparing HGSC to OSE, but there are only 1,107 DMCs and 3 DMRs when comparing HGSC to FTE
- Thus, the fewer differences between HGSC and FTE indicates that they have a more similar methylation landscape than that of HGSC and OSE
- Correlation analysis, principal component analysis, and hierarchal clustering also reveal that HGSC and FTE share a closer relationship than HGSC and OSE
- They also dug deeper into genes related to development and tissue specificity by zooming in on PAX8, mesothelin (MSLN), and Homeobox (HOX) genes, which further support the similarities between HGSC and FTE
In order to confirm their findings, the team also made use of a number of public data sets. Ultimately, since HGSC is often diagnosed too late, this methylomic understanding of its origins offers insight towards the development of improved diagnostics and therapeutics. It also provides a clever approach for tackling cancer’s tissue of origin.
Go uncover the origins of ovarian cancer in Molecular Cancer Research, September 2016