title: Making sense of intratumor genetic heterogeneity: altered frequency of androgen receptor CAG repeat length variants in breast cancer tissues.
abstract: 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.
authors: Lady Davis Institute for Medical Research, Montreal, Quebec, Canada. bruce.gottlieb@mcgill.ca
authors: Bruce
authors: B
authors: Gottlieb
authors: Carlos
authors: C
authors: Alvarado
authors: Chunlin
authors: C
authors: Wang
authors: Baback
authors: B
authors: Gharizadeh
authors: Farbod
authors: F
authors: Babrzadeh
authors: Brent
authors: B
authors: Richards
authors: Gerald
authors: G
authors: Batist
authors: Mark
authors: M
authors: Basik
authors: Lenore K
authors: LK
authors: Beitel
authors: Mark
authors: M
authors: Trifiro
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011944:Receptors, Androgen / Q000235:genetics*; D018911:Trinucleotide Repeats
chemical_list: D011944:Receptors, Androgen