Abstract
Malignant tumors behave dynamically as cell communities governed by ecological principles. Massive sequencing tools are unveiling the true dimension of the heterogeneity of these communities along their evolution in most human neoplasms, clear cell renal cell carcinomas (CCRCC) included. Although initially thought to be purely stochastic processes, very recent genomic analyses have shown that temporal tumor evolution in CCRCC may follow some deterministic pathways that give rise to different clones and sub-clones randomly spatially distributed across the tumor. This fact makes each case unique, unrepeatable and unpredictable. Precise and complete molecular information is crucial for patients with cancer since it may help in establishing a personalized therapy. Intratumor heterogeneity (ITH) detection relies on the correctness of tumor sampling and this is part of the pathologist’s daily work. International protocols for tumor sampling are insufficient today. They were conceived decades ago, when ITH was not an issue, and have remained unchanged until now. Noteworthy, an alternative and more efficient sampling method for detecting ITH has been developed recently. This new method, called multisite tumor sampling (MSTS), is specifically addressed to large tumors that are impossible to be totally sampled, and represent an opportunity to improve ITH detection without extra costs.
Highlights
Clear cell renal cell carcinoma (CCRCC) is nowadays a health problem of major concern in developed societies
Gerlinger et al [12] unveiled in 2012 to what extent this phenomenon is present in clear cell renal cell carcinomas, describing the molecular heterogeneity of these tumors across different regions within the same tumor
The performance of multisite tumor sampling (MSTS) to discover Intratumor heterogeneity (ITH) has proved to be superior at any time of tumor evolution and in all models compared with routine protocols [54]
Summary
Clear cell renal cell carcinoma (CCRCC) is nowadays a health problem of major concern in developed societies. The arrival of targeted therapies has increased the need of very precise information about ITH since it is observed in many tumor types and represents a major hurdle for effective therapy, provoking therapeutic resistance and metastatic recurrence [11]. In this sense, Gerlinger et al [12] unveiled in 2012 to what extent this phenomenon is present in clear cell renal cell carcinomas, describing the molecular heterogeneity of these tumors across different regions within the same tumor. This overview details a more advantageous alternative for tumor sampling supported by a in silico modeling with clinical validation
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