Dr Enrique Velazquez Villarreal - City of Hope, Duarte, USA

This study was about to understand the differences at ancestry level and we, right now, are focussing on colorectal cancer in Latino populations. We focussed on first generating clinical genomic data from our Hispanic community around our catchment area here in LA. So what we tried to understand here is if there is any difference in mutations in colorectal cancer from Latinos that basically have a difference in the tumour mutation burden. At this point we want to see if young people with colorectal cancer have different mutations than people that are more than 50 years old, or late onset colorectal cancer. So one of our main questions is to understand why Hispanic/Latinos in LA are experiencing high levels, high prevalence and high incidence, of colorectal cancer and this is our main question.

What was the study design?

We designed the study based on, first of all, go to the community, obtain tissue from different surgeries to extract parts of the tumour and then at some point using clinical genomic tools to analyse the genomic part and then integrate with the clinical data in order to better characterise the tumours. So the most important part here is that we characterise colorectal cancer tumours from early onset colorectal cancer in Hispanic/Latinos and once we obtain this information we identify that there is a difference between the early onset and the late onset at the mutation level. We don’t know if this will be a different biology but we just found a difference.

Now, beyond that we performed ancestry analysis in which each of our patients got an analysis of their genome and, based on this genome, basically we identified five superpopulations. So Americans, Africans, East Asians, South Asians and Caucasians. Based on these five superpopulations we identified that the individuals that have a higher percentage of genes pertaining to one specific superpopulation that is based on the Americans have a higher incidence in colorectal cancer, specifically early onset colorectal cancer. I think this is one of the  most important discoveries we have done until today in my lab.

What were the results of this study?

Yes, we identified also that specific genes like ABC, TP53, KRAS and even MYC had different frequencies. We compared to other studies worldwide, trying to understand if the standard Latino population in LA had a different tumour mutation burden and, of course, we identified differences at statistical significance, significant differences, and that’s really helped us to understand a little bit more about the biology.

Now, another important point that we did is about we performed a spatial transcriptomic analysis, we tried to understand at the very tissue level how different cells inside the tissue of the tumours are communicating. At some point there was a very interesting result where we identified that the stroma, the cancer cells and the immune cells have a very particular relationship that we are describing at this point and understanding more. We want to expand these results and increase our sample size and show more relevant and better discoveries according with this very top tier technology that is basically spatial transcriptomics in colorectal cancer. I will say that for the first time in this lab and this is probably one of the first studies in spatial transcriptomic colorectal cancer in Hispanic/Latinos where we are for the first time trying to understand this interaction of the immune cells, the stroma cells and the cancer cells in the tumour. When we studied for the first time this we described a very interesting biology never described before and this interaction will help us to target probably better therapies in order to attack these cancer cells that probably are having a different behaviour than other tumours in this specific population. Probably that’s the cause of the higher incidence and prevalence of colorectal cancer in the young population, in young Hispanic/Latinos in the LA area.

Is there anything else you would like to add?

I probably will say that when I talk about the AI conversational tool, one of the things that I want to highlight is we generated for the first time an artificial intelligence conversational tool that is a technology that helped us to have a conversation with a machine that in the background has terabytes of data, tonnes of files and tonnes of packages and tonnes of analysis already embedded that can help us to increase our chances for discovery and to understand better the biology and to identify better treatments and potential better therapies for cancer tumours