03/05/2019
Didier Jean’s research group of the “Functional Genomics of Solid Tumors – FunGeST” Team published an innovative way to take into account tumor heterogeneity in Malignant Pleural Mesothelioma.
Blum Y., Meiller C., Quetel L., Elarouci N., Ayadi M., Tashtanbaeva D., Armenoult L., Montagne F., Tranchant R., Renier A., de Koning L., Copin M. C., Hofman P., Hofman V., Porte H., Le Pimpec-Barthes F., Zucman-Rossi J., Jaurand M. C., de Reynies A., Jean D.
Dissecting heterogeneity in malignant pleural mesothelioma through histo-molecular gradients for clinical applications.
Malignant pleural mesothelioma (MPM) is recognized as heterogeneous based both on histology and molecular profiling. Histology addresses inter-tumor and intra-tumor heterogeneity in MPM and describes three major types: epithelioid, sarcomatoid and biphasic, a combination of the former two types. Molecular profiling studies have not addressed intra-tumor heterogeneity in MPM to date. Here, we use a deconvolution approach and show that molecular gradients shed new light on the intra-tumor heterogeneity of MPM, leading to a reconsideration of MPM molecular classifications. We show that each tumor can be decomposed as a combination of epithelioid-like and sarcomatoid-like components whose proportions are highly associated with the prognosis. Moreover, we show that this more subtle way of characterizing MPM heterogeneity provides a better understanding of the underlying oncogenic pathways and the related epigenetic regulation and immune and stromal contexts. We discuss the implications of these findings for guiding therapeutic strategies, particularly immunotherapies and targeted therapies.
This research work was performed thanks to a collaboration with “Cartes d’Identité des Tumeurs” program of the Ligue contre le Cancer and clinical departments of HEGP of Paris and the CHRU of Lille and Nice.