Document Detail

Making sense of intratumor genetic heterogeneity: altered frequency of androgen receptor CAG repeat length variants in breast cancer tissues.
MedLine Citation:
PMID:  23377847     Owner:  NLM     Status:  MEDLINE    
To examine the significance of intratumor genetic heterogeneity (ITGH) of the androgen receptor (AR) gene in breast cancer, patient-matched samples of laser capture microdissected breast tumor cells, adjacent normal breast epithelia cells, and peripheral blood leukocytes were sequenced using a novel next generation sequencing protocol. This protocol measured the frequency of distribution of a variable AR CAG repeat length, a functional polymorphism associated with breast cancer risk. All samples exhibited some degree of ITGH with up to 30 CAG repeat length variants identified. Each type of tissue exhibited a different distribution profile of CAG repeat lengths with substantial differences in the frequencies of zero and 18-25 CAG AR variants. Tissue differences in the frequency of ARs with each of these CAG repeat lengths were significant as measured by paired, twin t-tests. These results suggest that preferential selection of 18-25 CAG repeat length variants in breast tumors may be associated with breast cancer, and support the observation that shorter CAG repeats may protect against breast cancer. They also suggest that merely identifying variant genes will be insufficient to determine the critical mutational events of oncogenesis, which will require measuring the frequency of distribution of mutations within cancerous and matching normal tissues.
Bruce Gottlieb; Carlos Alvarado; Chunlin Wang; Baback Gharizadeh; Farbod Babrzadeh; Brent Richards; Gerald Batist; Mark Basik; Lenore K Beitel; Mark Trifiro
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2013-03-08
Journal Detail:
Title:  Human mutation     Volume:  34     ISSN:  1098-1004     ISO Abbreviation:  Hum. Mutat.     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-03-22     Completed Date:  2013-09-06     Revised Date:  2013-11-04    
Medline Journal Info:
Nlm Unique ID:  9215429     Medline TA:  Hum Mutat     Country:  United States    
Other Details:
Languages:  eng     Pagination:  610-8     Citation Subset:  IM    
Copyright Information:
© 2013 Wiley Periodicals, Inc.
Lady Davis Institute for Medical Research, Montreal, Quebec, Canada.
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MeSH Terms
Aged, 80 and over
Breast Neoplasms / genetics*,  pathology
Case-Control Studies
Genetic Variation*
Middle Aged
Neoplasm Grading
Neoplasm Staging
Receptors, Androgen / genetics*
Trinucleotide Repeats*
Reg. No./Substance:
0/Receptors, Androgen

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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