Transcriptomics of mussel transmissible cancer MtrBTN2 suggests accumulation of multiple cancerous traits and oncogenic pathways shared among bilaterians

Abstract

Transmissible cancer cell lines are rare biological entities giving rise to diseases at the crossroads of cancer and parasitic diseases. These malignant cells have acquired the amazing capacity to spread from host to host. They have been described only in dogs, Tasmanian devils and marine bivalves. The Mytilus trossulus Bivalve Transmissible Neoplasia 2 (MtrBTN2) lineage has even acquired the capacity to spread inter-specifically between marine mussels of the Mytilus edulis complex worldwide. To identify the oncogenic processes underpinning the biology of these atypical cancers we performed transcriptomics of MtrBTN2 cells. Differential gene expression, enrichment, protein-protein interaction network, and targeted analyses were used. Overall, our results suggests that the long-term evolution of MtrBTN2 has led to the accumulation of multiple cancerous traits. We also highlight that vertebrate and lophotrochozoan cancers share a large panel of common drivers, which supports the hypothesis of an ancient origin of oncogenic processes in bilaterians.

Genetic features of bivalve transmissible neoplasia in blue mussels from the Kola Bay (Barents Sea) suggest a recent trans‐Arctic migration of the cancer lineages

“…MtrBTN1 in 2016 and MtrBTN2 in 2019 (Yonemitsu et al, 2019), we have learned much about their prevalence, diversity and geographic distribution (Burioli et al, 2019(Burioli et al, , 2021Hammel et al, 2022Hammel et al, , 2023Riquet et al, 2017;Skazina et al, 2021Skazina et al, , 2023.…”

“…Several methods for diagnosing MtrBTNs have been mtDNA fragment spanning 16S rRNA and control region (CR) are the best markers for identifying both MtrBTN lineages (Yonemitsu et al, 2019). Quantitative PCR (qPCR) with primers specific for cancer-associated alleles at these loci has been developed (Burioli et al, 2021;Yonemitsu et al, 2019).…”

“…disease that first affects the haemolymph and eventually all the organs and tissues of the mollusc; cancer cells are released by diseased animals and spread through the water column (Burioli et al, 2021;Giersch et al, 2022).…”

Molecular diversity of bivalve transmissible neoplasia of blue mussels in the Kola Bay (Barents Sea) indicates a recent migration of the cancer lineages between the North Pacific and Northern Europe

“…Burioli et al (2023) have performed a transcriptomic study of Mtr BTN2, M. edulis from France and M. trossulus from the Kola Bay (three specimens of each). They found fixed differences in c.182 and c.821 between Mtr BTN2 and healthy mussels, which fits all the other data.…”

“…Polymorphism at the third position (c.392) was less informative for distinguishing MtrBTN but seemed to be informative for distinguishing M. edulis, on the one hand, and M. trossulus and MtrBTN, on the other hand, in the Kola Bay (Table 2). Burioli et al (2023) have performed a transcriptomic study of MtrBTN2, M. edulis from France and M. trossulus from the Kola Bay (three specimens of each). They found fixed differences in c.182 and c.821 between MtrBTN2 and healthy mussels, which fits all the other data.…”