Genomics

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Unique evolutionary trajectories of breast cancers with distinct genomic and spatial heterogeneity


ABSTRACT: To define the sources and the extent of heterogeneity, we performed an in-depth analysis of the genomic architecture of three chemoradiation-naïve breast cancers with well-defined clinical features including variable ER, PR, Her2 receptor expression and distinct pathogenic BRCA2mut genotypes. The latter included a germ line carrier and a patient with a somatic variant. In each case we combined DNA content-based flow cytometry with whole exome sequencing and genome wide copy number variant (CNV) analysis of distinct populations sorted from multiple (4-18) mapped biopsies within the tumors and involved lymph nodes. Interrogating flow-sorted tumor populations from each biopsy provided an objective method to distinguish fixed and variable genomic lesions in each tumor. Notably we show that tumors exploit CNVs to enrich fixed mutations and deletions that are shared throughout each tumor. The identification of fixed genomic lesions in distinct populations, that are shared or unique within each tumor, has broad implications for the study of tumor heterogeneity including the presence of tumor markers and therapeutic targets, and of candidate neoepitopes in breast and other solid tumors that can advance more effective treatment and clinical management of patients with disease.

ORGANISM(S): Homo sapiens

PROVIDER: GSE172262 | GEO | 2021/04/30

REPOSITORIES: GEO

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