Genetic Markers Found for Breast Cancer Brain Metastasis

The development of brain metastases from breast cancer depends on several prognostic factors, including younger age, ethnicity, and hormone receptor negative status.

Other factors include the presence of Breast cancer 1, early onset (BRCA1) germ-line mutations, and the expression of the epidermal growth factor receptor 2 (Her2/neu) proto-oncogene, all of which contribute to an increased rate of brain metastasis.

Scientists at the Translational Genomics Research Institute (Phoenix, AZ, USA) obtained 35 retrospective fresh-frozen samples of breast brain metastases from other institutes and as well as non-neoplastic brain samples, and10 non-neoplastic breast tissue specimens. A series of 50 early-stage breast cancer, grade 1 and 2, specimens were also obtained.

Genomic DNA (gDNA) was isolated from fresh-frozen tissue using the DNeasy Blood and Tissue Kit (Qiagen; Valencia, CA, USA) and total ribonucleic acid (RNA), including small RNA, was isolated using the mirVana miRNA Isolation Kit (Ambion; Austin, TX, USA). RNA samples were evaluated for integrity using the Bioanalyzer RNA 6000 Nano LabChip Kit on a Bioanalyzer 2400 (Agilent Technologies; Santa Clara, CA, USA). The team performed deep genomic profiling, integrating gene copy number, gene expression, and DNA methylation datasets on the collection of the 35 breast-brain metastases samples.

Some of the common genetic alterations identified in the study were gains and losses in chromosome 8, as well as cell proliferation and cell-cycle progression, key mechanisms of cancer caused by genetic alterations, linked to the genes Aurora A kinase (AURKA), Aurora B kinase (AURKB) and Forkhead box protein M1 (FOXM1). The authors concluded that genomic and epigenomic profiling of breast brain metastasis provided insight into the somatic events underlying this disease, which have potential in forming the basis of future therapeutic strategies. Using the PAM50 breast cancer intrinsic classifier, Luminal B, Her2+/ER negative, and basal-like tumors were identified as the most commonly represented breast cancer subtypes in the brain metastasis cohort.

Nhan L. Tran, PhD, an Associate Professor and senior coauthor of the study said, “This groundbreaking study sets the stage for more exacting exploration, using the latest genomic technologies and aimed at developing new therapies that could help the tens of thousands of patients who urgently need our help.” The study was published on January 29, 2014, in the journal Public Library of Science One.

Related Links:
Translational Genomics Research Institute
Qiagen
Ambion