Division of Cancer Genomics

Cancer genome: a molecular engine for robust and ever evolving ecosystem

Accumulation of genomic alterations in single cell is the start point of cancer. Even after the initial (ancestor) cancer clones are established, they continuously evolve by changing their genomes and clonal selection (so-called clonal evolution) to adapt with their harsh environments including anti-cancer therapies. Therefore, cancer is a disease of genomic evolution for achieving the fittest. Cancer genome presents spatiotemporal diversities, mutually interacts with microenvironments, and is a driving force of this evolutional process towards local optimization for survival.

A range of genetic alterations in the cancer genome, such as point mutations and structural rearrangements, are caused by combinations of stochastic events with aging and/or extrinsic (such as infection, smoking and exposures to various natural and chemical carcinogens) and/or intrinsic factors (DNA repair defects). By examining footprints of these genetic assaults on DNA (so-called mutational signature), we can trace backwards how cancer clones were generated and have evolved and diverged.

Egoistic non-self: host immune system and cancer genome

As cancer cells accumulate genetic alterations, they become more "non-self" compared to normal cells, and such abnormal cells should be eliminated by host immune surveillance. However, cancer cells further alter their genomes and/or modify immune environments, and escape from such systematic surveillance or attack. This could be regarded as "egoistic non-self" existed in the cancer genome, and is a very unique aspect of cancer.

The visions of our division

Division of Cancer Genomics aims comprehensive molecular genetic analyses of intractable cancers frequent in Japan and other Asian countries (Liver, Biliary tract and Gastric cancers), rare cancers (such as sarcoma, adult T cell lymphoma/leukemia, pediatric cancers), and other important cancers globally. Our primary goal is to identify molecular/genetic/immunological/microenvironmental features in each cancer type, to discover new therapeutic/diagnostic targets/makers/subclasses, to evaluate and uncover known and unknown carcinogens by mutational signature analysis for cancer prevention, and to tackle against cancer heterogeneity. We utilize new sequencing and other genome analytical technologies and histo-pathological knowledge for challenging these issues. Our group is a founding member of the International Cancer Genome Consortium (http://icgc.org), and a partner of Grand Challenge project (Mutographs of Cancer) (http://www.sanger.ac.uk/science/collaboration/mutographs-cancer-cruk-grand-challenge-project), and actively contributes to the international community. Our final goal is to understand cancer ecosystem molecularly and genetically, and make breakthroughs for cancer medicine and prevention with international collaborations.