Impact of germline susceptibility variants in cancer genetic studies

TL;DR

This paper emphasizes the importance of analyzing germline variants alongside somatic mutations in cancer studies to better understand genetic risk factors and tumor development.

Contribution

It provides a quantitative assessment of biases introduced when only somatic mutation data is used, highlighting the need to include germline information.

Findings

Germline variants influence cancer risk and tumor evolution.

Restricting analysis to somatic mutations can lead to biased conclusions.

Inclusion of germline data offers a more comprehensive understanding of cancer genetics.

Abstract

Although somatic mutations are the main contributor to cancer, underlying germline alterations may increase the risk of cancer, mold the somatic alteration landscape and cooperate with acquired mutations to promote the tumor onset and/or maintenance. Therefore, both tumor genome and germline sequence data have to be analyzed to have a more complete picture of the overall genetic foundation of the disease. To reinforce such notion we quantitatively assess the bias of restricting the analysis to somatic mutation data using mutational data from well-known cancer genes which displays both types of alterations, inherited and somatically acquired mutations.