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Status |
Public on Apr 30, 2021 |
Title |
Unique evolutionary trajectories of breast cancers with distinct genomic and spatial heterogeneity |
Organism |
Homo sapiens |
Experiment type |
Genome variation profiling by array
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Summary |
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.
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Overall design |
We applied DNA content based flow sorting to isolate the nuclei of clonal populations from multiple (4-18) biopsies from resected tumors from each of three breast cancer patients. We coupled this strategy with oligonucleotide array CGH (aCGH) and next generation sequencing, thereby obtaining high definition genomic profiles of clonal populations from each tumor. We identified fixed genomic lesions in each distinct population, including those that are shared or unique within each tumor. We then identified shared neoepitopes notably those arising from fixed shared variants in each tumor.
>>>Submitter states that raw data files for many samples are not available due to file loss.<<<
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Contributor(s) |
Phung T, Webster T, Lenkiewicz E, Malasi S, Andreozzi M, McCullough AE, Anderson KS, Pockaj BA, Wilson MA, Barrett MT |
Citation(s) |
34011996 |
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Submission date |
Apr 17, 2021 |
Last update date |
Jul 30, 2021 |
Contact name |
michael thomas barrett |
E-mail(s) |
barrett.michael@mayo.edu
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Phone |
480-301-6736
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Organization name |
mayo clinic arizona
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Street address |
13400 east shea boulevard
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City |
Scottsdale |
State/province |
Arizona |
ZIP/Postal code |
85259 |
Country |
USA |
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Platforms (1) |
GPL19387 |
Agilent-021850 SurePrint G3 Human CGH Microarray (Probe Name version) |
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Samples (40)
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Relations |
BioProject |
PRJNA722657 |