Every now and then my eye is caught by reports of new fusion genes being found in different cancers.  Often these descriptions involve researchers across multiple laboratories due to the rarity of the target.  Following a discussion on Twitter yesterday, a friend sent me the link to this interesting paper published in Science Translational Medicine.  Naturally, one of the first things that came to mind was ‘is the identified target druggable?’

Source: wikipedia micrograph of epithelioid hemangioendothelioma (from the liver)

Tanas et al., (2011) used deep gene sequencing and conventional cytogenetics to identify two genes involved in chromosomal translocation in epithelioid hemangioendothelioma (EHE), a rare vascular sarcoma that arises out of endothelial cells, namely:

  • WWTR1, WW domain-containing transcription regulator 1 (3q25) and
  • CAMTA1, calmodulin-binding transcription activator 1 (1p36).

The researchers noted that:

“CAMTA1 encodes a transcription factor that is found in all multi- cellular organisms tested and is evolutionarily conserved from Arabidopsis to humans.”

What is its function?

“Little is known about the protein’s function in mammalian cells, but in humans, the gene is expressed almost exclusively within the brain and has been implicated in memory because high amounts of CAMTA1 mRNA have been identified in memory-related regions.”

Now, there are a couple of other things to note:

  1. Not much is known about EHE, as the sarcoma was only described recently by Weiss and Goldblum (2008) in Enzinger and Weiss’s Soft Tissue Tumors. They appear to affect both sexes equally and are not age dependent, appearing in soft tissue, bone and visceral organs such as the liver and lungs.
  2. There are no current treatment options for EHE, other than surgical removal.
  3. Diagnosis of EHE is currently challenging and requires careful histological examination.

The paper is well worth reading for those interested in the challenges of fusion gene isolation, but what particularly struck me was the prevalence of the translocation in EHE compared with other sarcomas – it appears to be very distinctly different, since none of the others evaluated (nearly 30 of them, was found to have the translocation).

The presence of the fusion gene in EHE but not the other sarcomas strongly suggests a role in tumorigenesis, i.e. it’s an oncogene rather than a tumor suppressor gene.

“We anticipate that understanding the mechanism of WWTR1/CAMTA1 oncogenesis will be instrumental toward developing targeted therapy for EHE, for which none currently exists.”

There are some positive things that emerge from this research. In some ways, identification of the fusion gene in EHE may well change diagnosis and treatment options in the future for patients with the disease, much in the same way that imatinib helped to redefine the diagnosis and treatment of another rare sarcoma, gastrointestinal stromal tumours (GIST) in 2002.  Hope, as they say, is always just around the corner.

If any scientists or pharma people following this blog have something in their pipeline that may target the WWTR1/CAMTA1 fusion gene, then please let me know – it would be useful if we could crowdsource potential therapies aimed at oncogenes actively involved in tumorigenesis of rare cancers.

{UPDATE:  Bruce Shriver from the Liddy Shriver Sarcoma Initiative, patient support group since shared this link via Twitter on the background to the disease in plain English and further development of the fusion gene research – please check it out! }


ResearchBlogging.orgTanas, M., Sboner, A., Oliveira, A., Erickson-Johnson, M., Hespelt, J., Hanwright, P., Flanagan, J., Luo, Y., Fenwick, K., Natrajan, R., Mitsopoulos, C., Zvelebil, M., Hoch, B., Weiss, S., Debiec-Rychter, M., Sciot, R., West, R., Lazar, A., Ashworth, A., Reis-Filho, J., Lord, C., Gerstein, M., Rubin, M., & Rubin, B. (2011). Identification of a Disease-Defining Gene Fusion in Epithelioid Hemangioendothelioma Science Translational Medicine, 3 (98), 98-98 DOI: 10.1126/scitranslmed.3002409