Emerging patterns of somatic mutations in cancer

Abstract

The advance in technological tools for massively parallel, high-throughput sequencing of DNA has enabled the comprehensive characterization of somatic mutations in large number of tumor samples. Here, we review recent cancer genomic studies that have assembled emerging views of the landscapes of somatic mutations through deep sequencing analyses of the coding exomes and whole genomes in various cancer types. We discuss the comparative genomics of different cancers, including mutation rates, spectrums, and roles of environmental insults that influence these processes. We highlight the developing statistical approaches used to identify significantly mutated genes, and discuss the emerging biological and clinical insights from such analyses as well as the challenges ahead translating these genomic data into clinical impacts.

A critical analysis of cancer biobank practices in relation to biospecimen quality

“…Increased information at the genomic and transcriptomic level has also allowed researchers to understand the degree of inter-tumour heterogeneity that exists in diseases that were previously subject to much simpler classification systems (Vogelstein et al 2013;Watson et al 2013). The availability of transcriptomic and genomic data for large numbers of cancer biospecimens has enabled the identification of recurrent gene expression and sequence alterations in common cancer types (Watson et al 2013).…”

“…The availability of transcriptomic and genomic data for large numbers of cancer biospecimens has enabled the identification of recurrent gene expression and sequence alterations in common cancer types (Watson et al 2013). Similarly, many individual gene alterations are present in only small percentages of tumours diagnosed (Lawrence et al 2014).…”

Can we move towards personalised pancreatic cancer therapy?

“…As we better understand the molecular pathology of cancer, we are discovering substantial complexity, defining it as a composite of multiple diseases rather than the few previously defined morphologically [2].…”

Le rôle des phénomènes aléatoires dans le cancer

“…C'est notamment le cas des gènes dits « significativement mutés ». Ils sont appelés ainsi car leur mutation a joué un rôle moteur dans le développement de la maladie (d'où le terme mutation driver), et pour les distinguer des gènes dont les mutations n'ont pas de conséquence en termes d'avantage de croissance (mutation passenger) [2,31] (➜). Au sein de cet ensemble d'études de génomique, plusieurs observations sont à souligner : -un nombre élevé de mutations est généralement observé (de quelques centaines à quelques dizaines de milliers de mutations) [3], mais celles qui affectent la séquence des protéines sont beaucoup moins nombreuses [4] ; -ces études révèlent une forte hétérogénéité intertumorale : par exemple, parmi 100 tumeurs du sein, des mutations driver affectant au moins 40 gènes ont été observées, avec un total de 73 combinaisons différentes de gènes mutés [5].…”