Next generation DNA sequencing technologies have enabled the genome sequencing of an increasing number of tumour samples in recent years.
A recently published UK study presents data on more than 12,000 tumour genomes, providing detailed analysis of mutations found in the cancer samples (Degasperi, 2022).
Dávid Szüts, research group leader in the Institute of Enzymology, published a perspective article in the same issue of the journal Science, which puts the new results in context (Szüts, 2022). The unprecedented number of samples has allowed a more precise extraction of mutation patters found in tumours than any previous effort. The resulting mutational ‘signatures’ provide useful information about the causes of tumour development and, in some cases, aid treatment selection.
Dávid Szüts has been featured in Nature News as well, saying that researchers have probably now found all of the most common mutational signatures in cancer.
The Genome Stability research group, led by Dávid Szüts, is actively investigating the biological causes of mutagenesis in tumours, with breakthrough results recently published in prestigious journals. They have unravelled the genetic mechanisms of mutational processes caused by BRCA gene defects that predispose to breast and ovarian cancer (Chen, 2022), described the mechanism of a hitherto less known ‘collateral’ mutational process (Póti, 2022), and, in a US collaboration, precisely mapped the role of APOBEC enzymes, essential in antiviral defence, in tumour mutational processes (DeWeerd, 2022).
Chen D, Gervai JZ, Póti Á, Németh E, Szeltner Z, Szikriszt B, Gyüre Z, Zámborszky J, Ceccon M, d’Adda di Fagagna F, Szallasi Z, Richardson AL, Szüts D. (2022). BRCA1 deficiency specific base substitution mutagenesis is dependent on translesion synthesis and regulated by 53BP1. Nat Commun. 13, 226.
Degasperi A, Zou X, Dias Amarante T, Martinez-Martinez A. et al. (2022). Substitution mutational signatures in whole-genome–sequenced cancers in the UK population. Science 376, eabl9283.
DeWeerd RA, Németh E, Póti Á, Petryk N, Chen CL, Hyrien O, Szüts D, Green AM. (2022). Prospectively defined patterns of APOBEC3A mutagenesis are prevalent in human cancers. Cell Rep. 38, 110555.
Póti Á, Szikriszt B, Gervai JZ, Chen D, Szüts D. (2022). Characterisation of the spectrum and genetic dependence of collateral mutations induced by translesion DNA synthesis. PLoS Genet. 18, e1010051.
Szüts, D. (2022). A fresh look at somatic mutations in cancer. Science 376, 351-352.
Cover image: National Cancer Institute, Unsplash