Augusto Villanueva Rodriguez, MD, PhD Icahn School of Medicine at Mount Sinai New York, NY

Single Tumor Biopsies Can Overlook Liver Cancer’s Molecular Heterogeneity Interview with:

Augusto Villanueva Rodriguez, MD, PhD Icahn School of Medicine at Mount Sinai New York, NY

Dr. Villanueva Rodriguez

Augusto Villanueva Rodriguez, MD, PhD
Icahn School of Medicine at Mount Sinai
New York, NY What is the background for this study?

Response: There is limited understanding of the extent of molecular heterogeneity in liver cancer. This cancer is the second most lethal tumor and the fourth cause of cancer-related mortality worldwide.

Most patients diagnosed at advanced stages have a dismal survival, as most of them will develop resistance to systemic therapies. One of the potential mechanisms for this relates to the presence of different tumor clones within the same tumor nodule. This heterogeneity has been barely studied in liver cancer and our study provides a comprehensive analysis of the extent and potential clinical implications of intra-tumoral heterogeneity (ITH) in liver cancer. What are the main findings?

Response: The main findings of this study are that intra-tumoral heterogeneity has significant immune correlates, meaning that immune infiltration is associated with tumors that have altered (“edited”) clonal architectures. In addition, for some patients ITH implies a single tumor can hijack independent gene signaling networks depending on where a biopsy is taken. In other words, a single biopsy can radically mischaracterize the complete molecular profile of some liver tumors. In fact, such single liver tumors can be so molecularly variable that they reflect population level molecular diversity. What should readers take away from your report?

Response: Single tumor biopsies in a subset of patients with liver cancer may overlook significant molecular heterogeneity. One of the main drivers of this heterogeneity is the immune system which, by trying to destroy tumor cells, can significantly determine the composition of cancer clones present within a given tumor nodule. What recommendations do you have for future research as a result of this work?

Response: Tumor heterogeneity should be considered in any study developing novel biomarkers in liver cancer, particularly those aimed at predicting response to systemic therapies. Is there anything else you would like to add?

Response: Out study was among the first to apply single-cell RNA sequencing technologies to study different regions of the same tumor nodule.


Losic, B., Craig, A.J., Villacorta-Martin, C. et al. Intratumoral heterogeneity and clonal evolution in liver cancer. Nat Commun 11, 291 (2020) doi:10.1038/s41467-019-14050-z 


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Last Modified: Jan 16, 2020 @ 4:48 pm 

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