Reduce diagnosis times and have targeted and personalized drugs
July 22, 2020 - The evolution of papillary kidney carcinomas is at the center of a multicenter study conducted byUniversità Campus Bio-Medico di Roma in collaboration with international partners and recently published on Nature Communications. (DOI: 10.1038/s41467-020-16546-5). Papillary carcinomas represent approximately 10-15% of renal tumors which, in the last two decades, have recorded an annual increase in incidence of 2%, leading to approximately 99.200 new cases of renal carcinoma and 39.100 related deaths within the European Union in 2018. However, thanks to the ability to characterize the type of tumor more and more accurately, it is possible not only to reduce diagnosis times but also to have targeted and personalized drugs and protocols. It is precisely in this direction that the study is moving "The genomic and epigenomic evolutionary history of papillary renal cell carcinomas".
Through in-depth sequencing of the genome (so-called "whole genome sequencing"and "deep sequencing”) of multiple biopsy specimens in each patient's primary tumor and corresponding metastases, researchers studied the genetic alterations that drive the evolution of papillary kidney tumor (phylogeny), from its initial formation to metastases in other organs. These data made it possible to define genetic and epigenetic "signatures" of the various cellular components of the tumor (intratumor clonal heterogeneity). The analysis of tumor heterogeneity allows to better understand the history of the tumor and how it acquires new capabilities and aggressiveness over time.
“We deduced that the rate of mutations that drive carcinogenesis in these papillary tumors (driver mutations) is small and does not vary much over time - Explains Vito Michele Fazio, director of the Laboratory of Molecular Medicine and Biotechnology UCBM, among the creators and authors of the study -. Therefore, a single biopsy is sufficient to acquire useful and sufficient information to improve the diagnosis and define and guide a personalized therapy. Furthermore, understanding the molecular evolution of cancer has important implications for diagnosis and treatment. To date, renal tumors still lack a single genomic predictor of response to treatment and this research lays important prospective foundations for the development of new diagnostic markers and the identification of new molecular targets for drugs and targeted protocols, in the perspective of a medicine of precision and custom. The enormous number of molecular data obtained and archived represents a precious source of information from which further future analysis will open up new avenues for research, diagnosis and treatment of kidney cancer".
Together with the Laboratory of Molecular Medicine and Biotechnology UCBM the “Regina Elena” Cancer Institute of Rome, and the Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA, conceived and promoted the project. Due to the complexity and number of results obtained, in recent years the Oxford Big Data Institute, Oxford NIHR Biomedical Research Centre, UK has collaborated. Two former students are among the first signatories of the project UCBM, Prof. Maria Luana Poeta and Dr Manuela Costantini.
The research is part of the skills that the laboratory has developed on Next Generation Sequencing (NGS) and which has led to various collaborations for industrial research with leading Italian companies (DOI: 10.3390 / cancers11111691) and in the launch of a clinical molecular diagnostic service, based precisely on NGS.
