Brain cancer biology. Single-cell genomics. Mass General Hospital. Broad Institute.
Boston, MA
Joined July 2019
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Mario Suva retweeted
14/ This of course wouldn't have been possible without the generous contribution of the patients and their families, for which we are ever thankful.
Mario Suva retweeted
13/ Big thanks also to the institutions that provided tumor samples @DukeU, @MDAndersonNews, Tokyo University Hospital, Pitié-Salpêtrière Hospital, St. Michael's Hospital, Seoul National University and NORLUX and funders @NIH, @theNCI, Mark Foundation and Sontag Foundation.
Mario Suva retweeted
12/ Big thanks to the PIs that supervised the project @TiroshLab, @MarioSuva, @roelverhaak, Antonio Iavarone and Anna Lasorella, all collaborators and institutions involved in the CARE consortium @WeizmannScience, @MGHPathology, @broadinstitute, @YaleMed and @miamiuniversity.
Mario Suva retweeted
11/ To sum-up, our multi-center study offers a high-resolution atlas of GBM recurrence dynamics, shaped by treatment response and TME context and underscores the tremendous heterogeneity of this devastating disease.
Mario Suva retweeted
10/ Overall genetic divergence (SNVs + CNAs) correlated with transcriptional evolution, suggesting that GBM cell state shifts during recurrence are at least partially genomically driven.
Mario Suva retweeted
9/ Second, small deletion phenotype (linked to radiotherapy) was associated with hypoxia-related states at recurrence, likely reflecting selection of radioresistant subpopulations. SBS21 (MMR-deficiency signature) also increased post-treatment in both CARE and GLASS cohorts.
Mario Suva retweeted
8/ Interestingly, quantifying MGMT activity from the single-cell expression data outperformed promoter methylation as a prognostic marker in this cohort.
Mario Suva retweeted
7/ However, in certain sub-groups, specific trajectories do tend to recur more often. First, MGMT-Low tumors (likely TMZ responders) tend to lose MES-like states whereas MGMT-High tumors (likely non-responders) tend to gain MES-like at recurrence.
Mario Suva retweeted
6/ Despite global conservation, individual matched tumor pairs showed frequent divergence, with the majority switching at least one transcriptional layer. Overall, 72% of all possible transitions were observed across the cohort.
Mario Suva retweeted
5/ Contrary to previous studies, we did not observe a significant enrichment of mesenchymal-like (MES-like) states at recurrence. Instead, recurrence trajectories were diverse and patient-specific, with no single state dominating across the cohort.
Mario Suva retweeted
4/ And now for the results! Across the cohort the most consistent change at recurrence was reduced malignant cell fraction, with a reciprocal increase in glial and neuronal TME cells. This was observed in ~66% of patients, suggesting increased tumor integration into brain tissue.
Mario Suva retweeted
3/ We first leveraged this large cohort to revisit the intra- and inter-tumor heterogeneity in GBM and characterized three multi-layered transcriptional ecosystems. Read more about this study in this great thread by @Masashi →
nitter.cf/M_Nomura/status/192078…
1/ Thrilled to share our TWO back-to-back papers published in Nature Genetics today! nature.com/articles/s41588-0… , nature.com/articles/s41588-0…
Mario Suva retweeted
2/ In this study we profiled the longitudinal evolution of glioblastoma at single-cell resolution - altogether 121 treatment-naïve and exposed tumors from 59 patients, 430K nuclei, full clinical annotation and whole exome/genome sequencing.
Mario Suva retweeted
1/ Truly excited to share our new study that I had to privilege to co-lead during my PhD alongside great friends and collaborators @M_Nomura, Kevin C. Johnson and Luciano Garofano, which was published @NatureGenet!
nature.com/articles/s41588-0…
Mario Suva retweeted
Heterogeneity only now coming in view through large scale efforts - this clearly demonstrates how in #gbm and other heterogeneous cancers if we don’t study 100+ patients then we are not going to solve the problem. Thx to all for opp to contribute to this effort.
1/ Thrilled to share our TWO back-to-back papers published in Nature Genetics today! nature.com/articles/s41588-0… , nature.com/articles/s41588-0…
Mario Suva retweeted
13/ Also appreciate all collaborators, patients and their families who generously provided the samples.
Mario Suva retweeted
12/ Before that, I would like to say thank wonderful co-first authors, @AvishaySptizer, @Kevin_C_Johnson and @lucgar88. I thank my great mentor @MarioSuva and outstanding co-PIs @TiroshLab, @roelverhaak, Antonio Iavarone and Anna Lasorella.
Mario Suva retweeted
8/ Second, we describe the diversity of cellular states and their pathway-based functional activities, with an expanded set of malignant cell states, including glial progenitor cell-like, neuronal-like, and cilia-like states that were previously depleted by tumor dissociation
Mario Suva retweeted
10/ These three layers of heterogeneity are inter-related and partially associated with specific genetic aberrations, thereby defining three stereotypic ecosystems in GBM. This work provides an unparalleled view of the multi-layered transcriptional architecture of GBM.
