Whole genome and transcriptome analysis of metastatic adrenocortical carcinoma

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Published: 14 Feb 2019
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Dr Jean-Michel Lavoie - BC Cancer, Vancouver, Canada

Dr Jean-Michel Lavoie speaks to ecancer at the 2019 ASCO Genitourinary Cancers Symposium about a study looking at the whole genome and transcriptome analysis of metastatic adrenocortical carcinoma (mACC).

He reveals that among the findings of the analysis are a number of known mutations including mutations in pathways that affect the cell cycle and DNA damage repair that could suggest alternative treatments.

Dr Lavoie acknowledges that so far the information collected must be considered within the wider literature but that more and more information is being collected and that this could lead to clinical trials.

Adrenocortical cancer is a rare cancer and right now we only have really one standard treatment which is a combination of chemotherapy and a drug called mitotane. There is a need for more treatment in this setting. In Vancouver we have been doing a much larger initiative where we sequence the genome and a transcriptome that’s the product of those genes from patients with advanced cancers. So as part of that we sequenced six patients with adrenocortical cancer.

What methods were used in this study?

There are a number of studies out there that have used different methods for sequencing. Our approach is to do whole genome and transcriptome. So rather than having a panel based approach where you ask specific questions, we basically sequenced all the DNA in a sample and all the RNA.

What were the main findings from this study?

This is a small population and we have found a number of things that have been described by other groups. There are known mutations in these cancers and we have found a number of these. We have also found some mutations in pathways that affect the cell cycle and some mutations in DNA damage repair that may suggest different treatments.

How can these results guide the development of future treatments for mACC?

I think it’s a small piece of information that has to be put in the context of the larger literature out there. We’re still hopefully accumulating more and more information as we get more patients and as we get more data. Eventually this can lead to clinical trials that can be guided not just by the type of cancer but by what the genomic findings are. We’re still at a stage where we’re trying to describe the landscape of these cancers though.

To what extent does genetic variation between individual patients affect the results for this study?

I would say that we’re now just starting to understand that these cancers are very different from patient to patient and we have one cohort; there are other cohorts out there where the methods are a little bit different but essentially with the same overall aim of describing what are the genes driving those cancers. Ultimately we’re now understanding that there are a few key things that happen in a number of patients but patients, by and large from patient to patient, are very different. So that’s why it’s very challenging to do studies where all patients may be getting the same treatment when it may only be the appropriate treatment for a subset of those patients.

Did this study reveal any novel molecular changes that have not been mentioned in previous studies?

We found some alterations in cell cycle pathways and in DNA damage repair that had not been previously described in the literature.