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Series GSE172262 Query DataSets for GSE172262
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
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.
 
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.<<<
 
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
Submission date Apr 17, 2021
Last update date Jul 30, 2021
Contact name michael thomas barrett
E-mail(s) barrett.michael@mayo.edu
Phone 480-301-6736
Organization name mayo clinic arizona
Street address 13400 east shea boulevard
City Scottsdale
State/province Arizona
ZIP/Postal code 85259
Country USA
 
Platforms (1)
GPL19387 Agilent-021850 SurePrint G3 Human CGH Microarray (Probe Name version)
Samples (40)
GSM5251056 PS13-9062-F3-P4
GSM5251057 PS13-9062-F4-P5
GSM5251058 PS13-9062-F5-P6
Relations
BioProject PRJNA722657

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE172262_Breast_hetero-GEO_no_dups_.xlsx 198.8 Mb (ftp)(http) XLSX
GSE172262_RAW.tar 468.9 Mb (http)(custom) TAR (of TXT)
Processed data included within Sample table
Processed data are available on Series record

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