|Genomics is broadly defined as a discipline concerning the study
of the genomes of organisms, however, technically, it can have many
different forms depending on the molecular levels or aspects: variomics
focuses on sequence or structural variations, epigenomics on DNA or
histone modifications, cistromics on cis-elements for transcriptional
regulation, transcriptomics on transcribed genomic regions, and
interactomics on three-dimensional chromosomal interactions. In
medical research, cancer has become the “model disease” to receive
all the attention from the genomicists especially with the recent
development of high throughput sequencing technologies. In 2007, The
International Cancer Genome Consortium was launched to coordinate
a few synergetic efforts studying over 25,000 cancer genomes at the
genomic, epigenomic and transcriptomic levels . A public research
consortium named the Encyclopaedia of DNA Elements (ENCODE)
has also been launched to identify all functional elements in the human
genome using various cell types including a number of cancer cell
lines. Recently, methods of studying chromosomal interactions have
been coupled with high throughput sequencing, such as ChIA-PET 
and Hi-C , to analyse the interactomes of cancer cells.
|Despite the fact that cancer is the leading cause of death worldwide
and, thus, being in the limelight of the scientific arena, it is an exceptional
case of “gain-of-function” disease unlike other major organ-related
diseases that are mostly “loss-of-function”. The genomes within cells
accumulate mutations throughout life due to exposure to mutagens or
errors in replications. Some of these mutations can up-regulate growth
genes or down-regulate growth suppressor genes so the cells “gain”
advantages to grow and migrate and therefore become cancerous .
Nevertheless, some of these mutations may cause apoptosis or occur
in functional genes leading to loss-of-function. One example is from
the mice with a deficiency in CuZn superoxide dismutase (CuZnSOD).
Without the CuZnSOD to dismutate superoxide radicals generated in
the cytoplasm and nucleus, widespread oxidative damage and mutation
accumulation were observed in the liver of the mice that presumably
has a high oxygen metabolism and vulnerability to oxidative damage
[5-7]. As a result, the liver cells in these mice show more occurrences of
hepatocarcinogenesis and apoptosis, and reduced life span [5,6].
|Cancer genomics concentrates on the genomes of tumours, which
are effectively a “clonal population” of a single mutant cell, trying to
understand the transformation process. For organ genomics however,
a metagenomic approach has to be used because of the lack of clonal
expansion of the cell carrying the culprit mutation. A tissue sample
from a failing organ represents a mixture of cells bearing various types
of mutations, a portion of which cause the loss-of-function. The loss-offunction
mutations can be mutations accumulated to trigger apoptosis or mutations causing the dysfunction of organ-specific genes. The lossof-
function mutations should be commonly observed in the failing
organ samples collected from patient groups having a sufficient sample
size, although some apoptosis-causing mutations can be non-specific
(Figure 1). Together with epigenomic, cistromic, transcriptomic and
even interactomic sequencings, the nature of the mutations can be
|MKC is supported by British Heart Foundation.
- Hudson TJ, Anderson W, Artez A, Barker AD, Bell C, et al. (2010) International network of cancer genome projects. Nature 464: 993-998
- Birney E, Dutta A, Guigo R, Gingeras TR, Weng Z, et al. (2007) Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature 447, 799-816.
- Fullwood MJ, Liu MH, Pan YF, Liu J, Xu H, et al. (2009) An oestrogen-receptor-alpha-bound human chromatin interactome. Nature 462: 58-64.
- Lieberman-Aiden E, Van Berkum NL, Williams L, Imakaev M, Ragoczy T, et al. (2009) Comprehensive mapping of long-range interactions reveals folding principles of the human genome. Science 326: 289-293.
- Busuttil RA, Garcia AM, Cabrera C, Rodriquez A, Suh Y, et al. (2005) Organ-specific increase in mutation accumulation and apoptosis rate in CuZn-superoxide dismutase-deficient mice. Cancer Res 65: 11271-11275.
- Elchuri S, Oberley TD, Qi W, Eisenstein RS, Jackson Roberts L, et al. (2005) CuZnSOD deficiency leads to persistent and widespread oxidative damage and hepatocarcinogenesis later in life. Oncogene 24: 367-380.
- Huang TT, Yasunami M, Carlson EJ, Gillespie AM, Reaume AG, et al. (1997) Superoxide-mediated cytotoxicity in superoxide dismutase-deficient fetal fibroblasts. Arch Biochem Biophys 344: 424-432.