Additional Supporting Information may be found in the online version of this article.
Making Sense of Intratumor Genetic Heterogeneity: Altered Frequency of Androgen Receptor CAG Repeat Length Variants in Breast Cancer Tissues
Article first published online: 8 MAR 2013
© 2013 Wiley Periodicals, Inc.
Volume 34, Issue 4, pages 610–618, April 2013
How to Cite
Gottlieb, B., Alvarado, C., Wang, C., Gharizadeh, B., Babrzadeh, F., Richards, B., Batist, G., Basik, M., Beitel, L. K. and Trifiro, M. (2013), Making Sense of Intratumor Genetic Heterogeneity: Altered Frequency of Androgen Receptor CAG Repeat Length Variants in Breast Cancer Tissues. Hum. Mutat., 34: 610–618. doi: 10.1002/humu.22287
Communicated by Stephen J. Chanock
Contract grant sponsor: The Weekend to End Breast Cancer Fund of the Segal Cancer Centre of the Jewish General Hospital.
- Issue published online: 20 MAR 2013
- Article first published online: 8 MAR 2013
- Accepted manuscript online: 1 FEB 2013 11:34AM EST
- Manuscript Accepted: 14 JAN 2013
- Manuscript Received: 1 JUL 2012
- Jewish General Hospital
- intratumor genetic heterogeneity;
- breast cancer;
- androgen receptor;
- CAG repeat
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.