Bentham 2015 Abstract MiPschool London 2015

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Specific mitochondrial biogenesis patterns underlie development of breast cancer subtypes.

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Bentham RB, Menegollo M, Qin C, Yuneva M, Bryson K, Szabadkai G (2015)

Event: MiPschool London 2015

Cellular transformation and proliferation are fostered by a major rearrangement of cellular metabolism, resulting in unique expression patterns along a series of metabolic pathways in cancer. Mitochondria are central to many of these pathways, suggesting that the transcriptome underlying mitochondrial biogenesis will also follow a distinctive pattern in tumour tissues. Nonetheless, few studies have addressed this question so far.

In order to explore the expression pattern of nuclear encoded mitochondrial genes in cancer, we applied a novel bi-clustering algorithm together with supervised machine learning to predict gene correlations between mitochondrial genes and oncogenic pathways. In silico analysis of a large set of exome and mRNA expression data of BRCA in The Cancer Genome Atlas revealed a striking mosaic pattern of mitochondrial gene expression, which was specific to breast cancer subtypes. Functional validation of the bioinformatic analysis in subtype specific cancer cell line models showed unique mitochondrial metabolism correlating with gene expression profiles. Moreover, we have identified tumour subtypes of which the proliferation and survival relies on the expression of specific mitochondrial genesets, presumably driven by oncogene driven activation of transcriptional factors and co-regulators. The results provide a novel framework to understand the role of mitochondria in cancer and help to identify cancer subtypes that could be targeted by mitochondrion specific therapeutic approaches.


Labels: MiParea: Instruments;methods, mt-Biogenesis;mt-density, mtDNA;mt-genetics, mt-Medicine, Patients, mt-Awareness  Pathology: Cancer 







Affiliations

1-Dept Cell Developm Biol, Univ College London,UK. - robert.bentham.11@ucl.ac.uk

2-Dept Biomed Sc, Univ Padua, Italy

3-Nat Inst Med Res, London, UK

4-Dept Computer Sc, Univ College London, UK