Final Report Summary - TCAC IN CANCER (Defects in the tricarboxylic acid (KREBS) cycle genes in tumorigenesis) For the TCAC IN CANCER project, top European cancer research groups working on the association between defects in the Tricarboxylic acid cycle (TCAC) and cancer formed a consortium to: 1) profoundly characterise the human phenotypes to enable identification and efficient cancer prevention; and 2) to unravel the underlying molecular mechanisms. Previous breakthrough findings by the consortium participants and others had shown that defects in at least four TCAC genes - fumarate hydratase (FH, fumarase), and succinate dehydrogenase (SDH) B, C, and D - can confer susceptibility to cancer. We took these studies forward by characterising the natural history of the syndromes in large European cohorts. Simultaneously, we performed functional studies to elucidate the cellular events induced by these defects by systems biology approaches including functional studies in cell lines, model organisms, and transcription profiling of TCAC deficient and proficient tumours and models. TCAC defect associated expression patterns were utilised to examine other cancer types for such defects. We had evidence that modifying genes play a key role in TCAC defect associated tumourigenesis, and candidate regions had been identified. Vigorous efforts were conducted to identify the responsible genetic changes. The rationale to form this consortium was simple and strong. The consortium brought together the key European cancer researchers studying TCAC associated tumourigenesis. Studying separately the tumourigenic effects of FH and the different units of SDH would have been ineffective, and formation of the consortium enabled Europe to maintain the initiative in this new and exciting field of research. The deliverables arising from the work packages contribute to the common goals; prevention of TCAC associated cancers, and learning the lessons these lesions can teach to cancer research. Related documents Final Report - TCAC IN CANCER (Defects in the tricarboxylic acid (KREBS) cycle genes in tumorigenesis)
