New Techniques to Understand BHD Kidney Cancer

Birt-Hogg-Dubé syndrome (BHD) is associated with an increased risk of kidney cancer. Currently, people with BHD should get their kidneys monitored regularly to check for tumours. If these tumours reach 3 cm, surgery is done to remove them. However, there may be some situations where surgery isn’t appropriate. Therefore, there is a need to develop new treatment strategies for kidney cancer in BHD. To do this, we need a good understanding of how kidney cancer develops in BHD. This includes knowing which type of kidney cell the cancer came from and how these cells differ in their gene expression patterns.

A study published earlier this year looked at different inherited kidney cancers at a single cell level. This means looking at the individual cells that make up the cancer. They did this by taking samples from kidney tumours that were being surgically removed. In this study, there was one chromophobe kidney cancer tumour and one hybrid oncocytic chromophobe tumour (HOCT) from people with BHD. They then split the tumour into individual cells and used a technique called RNA sequencing.  This technique tells us which genes are turned on or off in cells. Doing this at a single cell level (instead of the entire tumour) allows us to know what is happening in each cell. This is important because tumours are complex and made up of many different cell types. A “map” can be created from the RNA sequencing data, where each cell is placed based on which genes are turned on in that cell. The cell type can be identified based on which genes were found. Cells that have similar genes turned on will be close to each other on the map. On this map, the researchers found that cells from BHD kidney cancers were close to a type of kidney cell called collecting duct. This suggests that BHD kidney cancers may originate from this cell type.

Next, the researchers looked at which genes were turned on specifically in the different types of BHD kidney cancer. It is common to only know which type of kidney cancer you have after surgery to remove the tumour. However, it may be useful to know which type of kidney cancer you have before treatment as this may influence the treatment you get. For example, different types of kidney cancer grow at different rates and some are more likely to spread than others. The researchers found that different genes were turned on/off in chromophobe cancer vs HOCT. In the future, a test may be able to look for these genes to identify which type of cancer a person has. Of particular interest, the authors of the study also identified a gene called MET found at high levels in BHD kidney cancers compared with other kidney cancers. There are already MET inhibitors that are approved for treating cancer, including kidney cancer. Therefore, the use of these inhibitors should be investigated further in BHD kidney cancer.

Altogether, this study used the latest technologies to further understand inherited kidney cancers. We look forward to seeing more research to understand how kidney cancer develops and how it can be treated in the future.