Our genome consists of 6 billion “letters” of DNA sequence that form “words” of different nature, such as "nouns" (genes), "verbs" (promoters) and "adjectives" (enhancers). These need to be organized into “sentences” to give rise to any particular “story”. Muscle, brain, bone and all other cells each emerge from unique "stories". The order of the “letters” does not typically change across different cell types. The key to generate muscle versus brain or other cell types is to fold our genome differently in each cell to re-align "words" and thereby create distinct "sentences" giving rise to unique "stories". In the process, some words are masked and therefore no longer part of the story. This folding process is guided by epigenetic events, literally events above (epi) our genome (genetics), that act like post-it notes to bookmark the regions of our genome that need to be read and those that are to be masked in any particular cell type.
In addition to genetic alterations (research theme 1), changes in the readability of “words” can alter stories to promote cancer development. This occurs through epigenetic events that will affect how the genome is folded or how particular "words" are masked.
A second research project in The Lupien Lab consists of mapping the epigenetic events discriminating the nature of “words” across cancer cell genomes. Through this approach the “stories” specific to cancer cells can be identified.
This approach was recently applied in colorectal cancer where significant differences in the maps of epigenetic events specific to enhancers [3
] (the adjectives) could be detected between normal colorectal crypt and cancer cells. This is also used to identify the mechanisms that promote cancer progression. Recent work from the Lupien Lab compared epigenetic maps from breast cancer cells responsive or resistant to hormonal (endocrine) therapy [4
]. Results revealed significant differences in all types of “words” that were masked and readable between drug-responsive and resistant breast cancer cells. This revealed a “story” specific to hormonal therapy-resistant breast cancer cells indicative of the activation of the Notch pathway. In agreement, drugs against the Notch pathway could block the growth of hormonal therapy-resistant breast cancer cells. On-going research is expanding this work to clinical samples.