Compelxo: identifying the missing heritability of breast cancer via next generation collaboration

Abstract

A proportion of the remaining unexplained genetic susceptibility to breast cancer is likely to be explained by many rare mutations in a large number of genes. Coordinated international collaboration offers great potential to advance the discovery of additional breast cancer susceptibility genes by increasing the likelihood of identifying functionally relevant genetic variants in the same genes in multiple families. A new consortium, COMPLEXO (a name chosen to reflect the complexity of the exome), has been formed to facilitate collaborations between researchers actively applying massively parallel sequencing to understand the genetics of breast and ovarian cancer. The aim of COMPLEXO is to bring to massively parallel sequencing the same power of large sample sets that have proven so successful in examining the role of common variants in cancer populations via the consortium model such as the Breast Cancer Association Consortium (BCAC), the Ovarian Cancer Association Consortium (OCAC) and the Collaborative Oncology Gene-environment Study (COGS). However, sequencing studies provide additional challenges in terms of defining specific modes of collaboration given differences in sequencing and targeted capture platforms, bioinformatics platforms, the need to integrate ongoing studies in many centers and socio-ethical-legal issues that are not as relevant to initiatives that are genotyping common genetic variation. These issues are relevant to research in all complex human diseases. We will describe our working and governance structures, our early experiences and ongoing activities aimed at identifying more of the missing heritability of breast cancer.