Genetics of Cancer: Past, Present, and Future

Cancer is a disease of aberrant cells which evade the cell cycle checkpoints for proliferation and resists apoptotic signals. A cancer cell is characterized by genetic instability, i.e., Nucleotide instability (NIN), microsatellite instability (MIN), chromosome instability (CIN). Cancer as a disease has been mentioned in ancient Greek, Indian, and Egyptian texts while the modern history of cancer genetics spans a period from 1800s to the present. The genetic causes of cancer have been increasingly identified in the past hundred years, while its epigenetic reasons have been recognized in the past few decades. Important discoveries made in 1900s had implications for cancer genetics; identification of Rous sarcoma virus as the first cancer-causing virus, role of X-rays in causing mutations in Drosophila, confirmation of DNA as the hereditary material and its molecular structure, the genetic code for protein, advent of the cell culturing techniques, and confirmation of exact number of chromosomes in a diploid human cell. Identification of oncogenes and tumor suppressor genes was followed by proving the role of chemical carcinogenesis and establishing chromosomal basis of neoplasia. The 2000s the identification of cancer stem cells, an improved detection of mutations based on techniques of whole genome sequencing, whole exome sequencing, and RNA sequencing also identified role of epigenome in the malignant phenotype. The Cancer Genome Atlas project in 2006 catalogued common genetic polymorphisms in genes and analysis of molecular changes in many cancers influenced the classification of cancer on the basis of tissue of origin and the molecular changes. The research in cancer genetics in the past few decades has indicated an essential role of epigenetic modifications, mutations and modifications in histones, the role of micro-RNAs and long non-coding RNAs, and changes in architecture of chromatin, in the origin and progression of a cancer with implication for future therapeutic regimes.