Sarhadi, Shamim and Salehzadeh-Yazdi, Ali and Damaghi, Mehdi and Zarghami, Nosratollah and Wolkenhauer, Olaf and Hosseini, Hedayatollah (2020) Omics Integration Analyses Reveal the Early Evolution of Malignancy in Breast Cancer. CANCERS, 12 (6): 1460. ISSN , 2072-6694
Full text not available from this repository. (Request a copy)Abstract
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 over the pre- and post-invasive pathological stages. Indeed, further genetic alterations in later stages do not establish de novo malignancy routes; however, they serve to fine-tune antecedent signaling pathways.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CARCINOMA IN-SITU; DUCTAL CARCINOMA; EARLY DISSEMINATION; TUMOR EVOLUTION; HETEROGENEITY; METASTASIS; MUTATIONS; NETWORKS; PLATFORM; DATABASE; breast cancer; cancer evolution; omics data integration; machine learning; forward and backward evolution |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für experimentelle Medizin und Therapieverfahren |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 22 Mar 2021 12:04 |
| Last Modified: | 22 Mar 2021 12:04 |
| URI: | https://pred.uni-regensburg.de/id/eprint/44450 |
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