Genome evolution during progression to breast cancer
Daniel E Newburger1, Dorna Kashef-Haghighi, Ziming Weng
1Biomedical Informatics Training Program, Stanford, California 94305, USA.
Genome Research
|April 10, 2013
Summary
Genomic analysis of early breast neoplasias reveals that common ancestors with aneuploidies may predispose tissue to cancer. Carcinoma evolution accelerates due to increased cell division, not specific mutations.
Area of Science:
- Genomics
- Cancer Biology
- Breast Cancer Research
Background:
- Cancer evolution involves genomic damage, epigenetic changes, and proliferation leading to carcinoma.
- Early neoplasias are precursor stages to carcinomas, distinct from normal breast tissue.
Purpose of the Study:
- To elucidate the role of early neoplasias in cancer evolution.
- To infer the order, timing, and rates of genomic events in breast cancer development.
Main Methods:
- Comparative whole-genome sequencing of early neoplasias, matched normal tissue, and carcinomas from six patients (31 samples total).
- Utilized somatic mutations as lineage markers to construct phylogenetic trees within each patient.
- Inferred genomic event order, timing, and rates based on lineage trees.
Main Results:
- In 4/6 cases, early neoplasia and carcinoma shared a common ancestor with recurring aneuploidies.
- Carcinoma lineages exhibited accelerated evolution in all six cases.
- Somatic mutation transition spectra were stable, suggesting increased cell division, not specific mutational mechanisms, drives mutation accumulation.
- Neither early neoplasia nor carcinoma genomes were enriched with functional somatic point mutations.
Conclusions:
- Aneuploidies in common ancestors of neoplastic and tumor cells represent early events impacting numerous genes.
- These early aneuploidies may predispose breast tissue to invasive carcinoma development.
- Carcinoma evolution is characterized by accelerated proliferation rather than specific mutational signatures.
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