Our limited knowledge of the genetic basis of cancer diseases based on candidate gene approaches has now been expanded by the use of massive parallel sequencing (MPS). These have helped to uncover the genomic landscape of cancers showing that, beyond high frequency mutations, a plethora of different molecular features are identified at low frequency and define cancer molecular subgroups of clinical interest. Recent works exploring the molecular variations’ landscape of different cancers have also highlighted a high degree of genetic heterogeneity in metastatic deposits, which substantially reflects the presence of different subclones within the primitive disease. When ignored, molecular heterogeneity can lead to failure in therapeutic treatments, as drugs that may have efficacy in subgroups of patients with specific molecular phenotypes may show marginal response when tested in a large group of unselected patients. This calls for the revisitation of the classical pathological diagnosis of cancer where the description of intra-tumor heterogeneity at both morphological and molecular level are taken into account for a diagnoistic report to be clinically useful to devise first, second and additional therapeutic choices.

Aldo Scarpa is professor of Pathology and Molecular Pathology. He is the Director of the Department of Pathology and Diagnostics (www.dpd.univr.it) and Director of the ARC-NET Research Centre for Applied Research on Cancer at the University and Hospital Trust of Verona (www.arc-net.it). Dr. Scarpa received his MD from the University of Padova, and his PhD in Molecular Pathology from the University of Verona. Early in his medical career he served as a family practitioner and thereafter as deputy director of the Clinical Pathology Laboratory of the Military Hospital of Verona before completing his Residency in Pathology at the University of Parma. His career includes extended periods in renowned Institutions in Italy Europe, United States of America, and Japan where has spent one year at the National Cancer Center of Tokyo. Dr. Scarpa has been a pioneer since the early ’80s in the application of molecular biology to the study of cancer. He founded Molecular Diagnostic Laboratories at Verona University (1990) and at the Cancer Centre in Cuenca-Ecuador (2001), performing population screening for cervical cancer using papilloma DNA testing, molecular diagnosis of leukemias and cancers for therapy decisions and follow up as well as characterization and monitoring of bone marrow transplantation. He is a proponent of biobanking, having begun tissue collections and cancer modelling in early 80’s. His research interests focus on cancer pathology and genetics and his work has been published in over 250 peer-reviewed publications. He is the Leader of the Italian project within the International Cancer Genome Consortium.