Genomic tumor evolution of breast cancer

Abstract

Owing to recent technical development of comprehensive genome-wide analysis such as next generation sequencing, deep biological insights of breast cancer have been revealed. Information of genomic mutations and rearrangements in patients' tumors is indispensable to understand the mechanism in carcinogenesis, progression, metastasis, and resistance to systemic treatment of breast cancer. To date, comprehensive genomic analyses illustrate not only base substitution patterns and lists of driver mutations and key rearrangements, but also a manner of tumor evolution. Breast cancer genome is dynamically changing and evolving during cancer development course from non-invasive disease via invasive primary tumor to metastatic tumor, and during treatment exposure. The accumulation pattern of base substitution and genomic rearrangement looks gradual and punctuated, respectively, in analogy with contrasting theories for evolution manner of species, Darwin's phyletic gradualism, and Eldredge and Gould's "punctuated equilibrium". Liquid biopsy is a non-invasive method to detect the genomic evolution of breast cancer. Genomic mutation patterns in circulating tumor cells and circulating cell-free tumor DNA represent those of tumors existing in patient body. Liquid biopsy methods are now under development for future application to clinical practice of cancer treatment. In this article, latest knowledge regarding breast cancer genome, especially in terms of 'tumor evolution', is summarized.

Mechanisms behind the Resistance to Trastuzumab in HER2-Amplified Breast Cancer and Strategies to Overcome It

“…These studies have some limitations, such as the limited statistical power to allow multiple comparisons, the difficulty of obtaining adequate tumor samples from all patients, and the possible changes in expression and mutational profile, which a tumor can experience throughout its evolution. 10 The last circumstance could be relevant in those trials performed in the relapse time with tumor samples available only from the primary tumor.…”

Phylogenetic Tree Inference: A Top-Down Approach to Track Tumor Evolution

“…Genomic variations in cancer cells gradually accumulate over the course of carcinogenesis and cancer development (Gerlinger et al, 2012;Sato et al, 2016). So despite the complexity in cancer evolution, more than two ways split is rarely observed on the evolutionary tree in existing studies (Hong et al, 2015;Schwarz et al, 2015;Brown et al, 2017).…”

Cancer as a result of genetic mosaicism

“…Появилась концепция прерывистого равновесия (punctuated equilibrium), согласно которой биологическое развитие может происходить скачками (квантами), перемежающимися длительными периодами покоя [63,64]. С некоторым запозданием такая же смена парадигм произошла и в фундаментальной онкологии [65][66][67][68][69][70][71]. Так, полногеномное секвенирование «раковых» геномов обнаруживает наряду с «медленным» сценарием (в русле концепции многостадийного канцерогенеза) еще и «быстрый» (в соответствии с концепцией прерывистого равновесия) (см.…”