Aggressive triple negative breast cancers have unique molecular signature on the basis of mitochondrial genetic and functional defects.

Aggressive triple negative breast cancers have unique molecular signature on the basis of mitochondrial genetic and functional defects. Biochim Biophys Acta. 2018 Jan 05;: Authors: Guha M, Srinivasan S, Raman P, Jiang Y, Kaufman BA, Taylor D, Dong D, Chakrabarti R, Picard M, Carstens RP, Kijima Y, Feldman M, Avadhani NG Abstract Metastatic breast cancer is a leading cause of cancer-related deaths in women worldwide. Patients with Triple Negative breast cancer (TNBCs), a highly aggressive tumor subtype, have a particularly poor prognosis. Multiple reports demonstrate that altered content of the multicopy mitochondrial genome (mtDNA) in primary breast tumors correlates with poor prognosis. We earlier reported that mtDNA copy number reduction in breast cancer cell lines induces an epithelial-mesenchymal transition associated with metastasis. However, it is unknown whether the major breast tumor subtypes (TNBC, Luminal and HER2+) differ in the nature and amount of mitochondrial defects and if mitochondrial defects can be used to identify tumors at risk for metastasis. By analyzing human primary tumors, cell lines and the TCGA dataset, we demonstrate a high degree of variability in mitochondrial defects among the tumor subtypes and TNBCs, in particular, exhibit higher frequency of mitochondrial defects, including reduced mtDNA content, mtDNA sequence imbalance (mtRNR1:ND1 or mtRNR1:ND4), impaired mitochondrial respiration and metabolic sw...
Source: Biochimica et Biophysica Acta - Category: Biochemistry Authors: Tags: Biochim Biophys Acta Source Type: research