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Making Sense of Intratumor Genetic Heterogeneity: Altered Frequency of Androgen Receptor CAG Repeat Length Variants in Breast Cancer Tissues
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2013 (English)In: Human Mutation, ISSN 1059-7794, E-ISSN 1098-1004, Vol. 34, no 4, 610-618 p.Article in journal (Refereed) Published
Abstract [en]

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 1825 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 1825 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.

Place, publisher, year, edition, pages
2013. Vol. 34, no 4, 610-618 p.
Keyword [en]
Androgen receptor, Breast cancer, CAG repeat, Intratumor genetic heterogeneity
National Category
Genetics
Identifiers
URN: urn:nbn:se:kth:diva-146833DOI: 10.1002/humu.22287ISI: 000316629000011PubMedID: 23377847Scopus ID: 2-s2.0-84875494277OAI: oai:DiVA.org:kth-146833DiVA: diva2:725523
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QC 20140616

Available from: 2014-06-16 Created: 2014-06-16 Last updated: 2017-12-05Bibliographically approved

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