Document Detail


Genomic (in)stability of the breast tumor microenvironment.
MedLine Citation:
PMID:  23038813     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The breast tumor microenvironment plays an active role in tumorigenesis. Molecular alterations have been identified in tumor-associated stroma; however, there is considerable debate as to whether the stroma is characterized by genomic instability or whether detection of chromosomal alterations reflects technological artifact rather than the true genomic content of the tumor microenvironment. Thus, breast stroma specimens from 112 women undergoing reductive mammoplasty (n=7), prophylactic mastectomy (N=6) or mastectomy for a breast disease (n=99) were frozen in optimal cutting temperature medium. Allelic imbalance (AI) analysis was performed using a panel of 52 microsatellite markers in 484 stromal specimens from 98 women, of which 92% had no detectable AI events. When compared to previously generated AI data from 77 formalin-fixed, paraffin-embedded (FFPE) stroma specimens, 42% of which harbored at least one detectable AI event, the frequency of AI in the FFPE specimens (4.62%) was significantly higher (P<0.001) than that found in frozen specimens (0.45%). This comparison of AI between FFPE and research-grade specimens suggests that past reports of AI in breast stroma reflect artifact in the archival specimens caused by formalin-fixation, paraffin-embedding and tissue storage. Furthermore, SNP data was generated from a subset of 86 stromal specimens using SNP array and copy number alterations were identified using Partek Genomics Suite. For 95% of the specimens, no detectable copy number alterations were found and the 11 changes that were detected were small and not shared between specimens. These data, therefore, support a model in which the tumor microenvironment is genetically stable.
Authors:
Seth Rummel; Allyson L Valente; Jennifer L Kane; Craig D Shriver; Rachel E Ellsworth
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-4
Journal Detail:
Title:  Molecular cancer research : MCR     Volume:  -     ISSN:  1557-3125     ISO Abbreviation:  Mol. Cancer Res.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-5     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101150042     Medline TA:  Mol Cancer Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Windber Research Institute.
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