All those exons and MAX

It is now a good time to do translational research on pheo. A clinician/researcher myself, I am following pheo research closely and I can tell that translational research on pheo is getting great results.

Translational research directly addresses mechanisms of human diseases. Translational research is the interface between basic and clinical research. The recent boom in translational research, in my opinion, is driven by two forces: patient advocacy groups and new technologies. Patient advocacy groups are more like corporate now. They usually hire MBAs to manage their operations and use more sophisticated strategies to advance their causes. New technologies are being developed almost every day. The new technologies need to find applications to show they are worthwhile in answering medical questions. With the synergy of those two forces, new technologies are more and more applied to less common diseases. Compared with common diseases, less common diseases, such as pheo, are more easily studied with the new technologies because they are more homogeneous. For example, there are so many types of prostate cancer, making a common etiology less likely. While pheo, by virtue of its rarity and uniform pathology, share more common features between each other.

One such new technology, exonomics, sequences almost every exon of the genome. Exons are the DNA stretches that actually encode proteins. (Introns, on the other hand, are DNA stretches that do not.) Because proteins are the doers and movers of biology, sequencing the exons likely yields insight of genetic causes of diseases.

Today, I noted a paper just published online which identifies a new tumor suppressor gene for pheo called MAX. The Spanish doctors include 3 families of familial pheo who do not have any mutations in known genes important for pheo. The exons of a lot of genes are sequenced in this study and MAX mutations appear to cause pheo in the 3 families. Now the list of pheo genes is getting even longer: RET, VHL, SDHA, SDHB, SDHC, SDHD, SDHAF2, NF1, TMEM127, and MAX. Does this mean we have to sequence every gene in all patients? Of course not. Each patient’s unique family history and pheo presentation are still the basis for clinical care. Rather, this study demonstrates the power of careful translational research. For such research to be successful, the clinicians must identify a group of patients that share key common clinical features. Scientists, on the other hand, must know all the details of the technology and sieve through the data to find the real molecular deficit. The importance of patient participation of such research cannot be overemphasized.

Dr. Pheo