Use of signals of positive and negative selection to distinguish cancer genes and passenger genes

Abstract

A major goal of cancer genomics is to identify all genes that play critical roles in carcinogenesis. Most approaches focused on genes that are positively selected for mutations that drive carcinogenesis and neglected the role of negative selection. Some studies have actually concluded that negative selection has no role in cancer evolution. In the present work we have re-examined the role of negative selection in tumor evolution through the analysis of the patterns of somatic mutations affecting the coding sequences of human genes. Our analyses have confirmed that tumor suppressor genes are positively selected for inactivating mutations. Oncogenes, however, were found to display signals of both negative selection for inactivating mutations and positive selection for activating mutations. Significantly, we have identified numerous human genes that show signs of strong negative selection during tumor evolution, suggesting that their functional integrity is essential for the growth and survival of tumor cells.

DNA Profiling of ING1 Gene in Triple Negative Breast Cancer

“…This means that in many distinct tumor types, its expression is lost or significantly diminished (Ythier et al, 2008;Li et al, 2011b). According to a study, the epigenetic regulator ING1 may engage in new cell functions when expressed at high levels ( Thakur et al, 2012), and a study on the ING1 gene has offered strong support for its function as a tumor suppressor in the development of cancer (Bányai et al, 2021).…”

Smoke-induced SAV1 Gene Promoter Hypermethylation Disrupts YAP Negative Feedback and Promotes Malignant Progression of Non-small Cell Lung Cancer

“…Mechanically, lung cancer cells taken from the lungs of smokers contain “drive” EGFR mutations and many other “passenger” mutations. These passenger genes may modify signal transduction pathways, making it more difficult to induce cell death with EGFR-TKIs therapy alone 43 , 44 . In our study, it was found that the expression of SAV1 in lung cancer tissue of smoking patients was significantly lower than that of non-smoking patients, and the lentivirus-mediated SAV1 gene transfer could inhibit the growth of NSCLC cells and organoids, especially in smoking patients.…”

Single-Cell RNA Sequencing Approaches for Tracing T Cell Development

“…During cancer and disease progression, genetic changes including deletions, substitutions, and translocations can result in an altered cell state (96). An understanding of gene mutations that affect T cell development is important for addressing diseases caused by altered T cell development, such as T cell leukemia (12,97). Direct nuclear tagmentation RNA-seq allows for integration of scRNA-seq data with whole genome sequence (98).…”