Cancers, Vol. 12, Pages 1460: Omics Integration Analyses Reveal the Early Evolution of Malignancy in Breast Cancer

Cancers, Vol. 12, Pages 1460: Omics Integration Analyses Reveal the Early Evolution of Malignancy in Breast Cancer Cancers doi: 10.3390/cancers12061460 Authors: Shamim Sarhadi Ali Salehzadeh-Yazdi Mehdi Damaghi Nosratollah Zarghami Olaf Wolkenhauer Hedayatollah Hosseini The majority of cancer evolution studies involve individual-based approaches that neglect the population dynamics necessary to build a global picture of cancer evolution for each cancer type. Here, we conducted a population-based study in breast cancer to understand the timing of malignancy evolution and its correlation to the genetic evolution of pathological stages. In an omics integrative approach, we integrated gene expression and genomic aberration data for pre-invasive (ductal carcinoma in situ; DCIS, early-stage) and post-invasive (invasive ductal carcinoma; IDC, late-stage) samples and investigated the evolutionary role of further genetic changes in later stages compared to the early ones. We found that single gene alterations (SGAs) and copy-number alterations (CNAs) work together in forward and backward evolution manners to fine-tune the signaling pathways operating in tumors. Analyses of the integrated point mutation and gene expression data showed that (i) our proposed fine-tuning concept is also applicable to metastasis, and (ii) metastases sometimes diverge from the primary tumor at the DCIS stage. Our results indicated that the malignant potency of breast tumors is constant ove...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research