Correction: Somatic mutations in cancer development

Lucio Luzzatto

doi:10.1186/1476-069x-10-s1-s16

Abstract

Since publication of Environmental Health 2011, 10(Suppl 1):S12 [1] it has been noticed that titles and captions for the figures and tables were incorrectly applied. In this full-length correction article, figures and tables have been renumbered with legends and captions applied appropriately. Some minor typographical errors have also been corrected. The inconvenience caused to readers by premature publication of the original paper is regretted.The transformation of a normal cell into a cancer cell takes place through a sequence of a small number of discrete genetic events, somatic mutations: thus, cancer can be regarded properly as a genetic disease of somatic cells. The analogy between evolution of organisms and evolution of cell populations is compelling: in both cases what drives change is mutation, but it is Darwinian selection that enables clones that have a growth advantage to expand, thus providing a larger target size for the next mutation to hit. The search for molecular lesions in tumors has taken on a new dimension thanks to two powerful technologies: the micro-arrays for quantitative analysis of global gene expresssion (the transcriptome); and ‘deep’ sequencing for the global analysis of the entire genome (or at least the exome). The former offers the most complete phenotypic characterization of a tumor we could ever hope for – we could call this the ultimate phenotype; the latter can identify all the somatic mutations in an individual tumor – we could call this the somatic genotype. However, there is definitely the risk that while we are ‘drowned by data, we remain thirsty for knowledge’. If we want to heed the teachings of Lorenzo Tomatis, I think the message is clear: we ought to take advantage of the new powerful technologies – not by becoming their slaves, but remaining their masters. Identifying somatic mutations in a tumor is important because through a deeper understanding of the nature of that particular tumor it can help us to optimize therapy or to design new therapeutic approaches.

Highlights

Lorenzo Tomatis was a towering figure in the study of cancer and cancer epidemiology: not just because from 1982 to 1993 he was the Director of the International Agency for Research against Cancer (IARC), but even more because he commanded immense international respect as a scientist ahead of his time in the understanding of the environmental causes of cancer
My job today is to discuss the role of somatic mutations in oncogenesis
Using a timehonoured terminology of medicine, if heredity and environment are the aetiology of cancer, somatic mutations are the essence of its pathogenesis

Summary

Introduction

My job today is to discuss the role of somatic mutations in oncogenesis. In a nutshell, and using a timehonoured terminology of medicine, if heredity and environment are the aetiology of cancer, somatic mutations are the essence of its pathogenesis. Over the past 4 years, genome-wide association studies (GWAS) have become very popular: this is not a conceptually new approach, as it is merely an updated version of (iv), but it is made much more powerful through the availability of some millions single nucleotide polymorphisms (SNPs) Thanks to this increased power, many low penetrance genes or loci have been identified, that affect the risk of individual types (or several types) of cancer – mostly by less than +/- 30% – in one or another population The rate of somatic mutations – and the risk of cancer – can be increased by inherited genes or by environmental agents, as we have outlined; somatic mutations occur all the time as spontaneous stochastic events, because the replication of DNA is extremely faithful but not perfect: this means that there is always an element of chance in oncogenesis (Figure 8) In this respect, we know surprisingly little about the. Much recent literature gives the impression that there is a surplus of information, from gene expression profiles

Luzzatto L

32. Esteller M