An epigenetic difference in twins explains the different risk of breast cancer
Monozygotic twins have the same genome, in other words, the same DNA molecule in both siblings. Despite being genetically identical, both twins may have different diseases at different times. This phenomenon is called twin discordance. But how is it possible that people who have the same genetic sequence present different pathologies and at different ages? The explanation partly lies in the fact that the chemical signals added in the DNA to "switch off" or "switch on" genes can be different. These signals are known as epigenetic marks.
Monozygotic twins have the same genome, in other words, the same DNA molecule in both siblings. Despite being genetically identical, both twins may have different diseases at different times. This phenomenon is called twin discordance. But how is it possible that people who have the same genetic sequence present different pathologies and at different ages? The explanation partly lies in the fact that the chemical signals added in the DNA to "switch off" or "switch on" genes can be different. These signals are known as epigenetic marks.
The research team led by Manel Esteller, researcher at ICREA at the Faculty of Medicine and director of the Cancer Epigenetics and Biology Program at the Bellvitge Biomedical Research Institute (IDIBELL), affiliated centres with the UB health campus, HUBc, studied the levels of DNA methylation (the best known epigenetic mark) in the blood of 36 pairs of twins diagnosed with breast cancer or healthy. The study identified an epigenetic change in the twin who will develop breast cancer but not in the healthy one. The finding has been published this week in the journal Carcinogenesis.
Researchers analyzed half a million pieces of the genome in each twin and compared them; they found that women who have developed breast tumours showed a pathological gain of methylation in the DOK7 gene. "An epigenetic alteration associated with an increased risk of breast cancer can be detected in the sick twin a few years before the clinical diagnosis", said Dr Esteller.
The next step to be taken by researchers is to know the exact function of the DOK7 gene. "We believe it is a regulator of tyrosine kinases, an antitumor drug target already used for the treatment of breast cancer. If DOK7 performs this function, new studies to test drugs with tumour chemopreventive effects in breast cancer could be planned in the future", concludes the research coordinator.
Article reference
Heyn H., Carmona F. J., Gomez A., Ferreira H. J., Bell J. T., Sayols S., Ward K., Stefansson O. A., Moran S., Sandoval J., Eyfjord J.E., Spector T.D., Esteller M. “DNA methylation profiling in breast cancer discordant identical twins identifies DOK7 as novel epigenetic biomarker”. Carcinogenesis, October 2012. [Published online]