Research teams led by the Wellcome Trust Sanger Institute announced that they have sequenced the malignant melanoma and lung cancer cell genomes. Their data has been reported in back to back publications in this months issue of Nature. The studies reveal for the first time essentially all the mutations in malignant melanoma and lung cancer.
To map the cancer genomes, the researchers sequenced a small-cell lung cancer cell line called, NCI-H209, as well as the genomes of a malignant melanoma and lymphoblastoid cell line obtained from the same person. They found more than 30,000 gene mutations in the malignant melanoma cells. Whereas, in the H209 small-cell lung cancer cells, they found over 23,000 genetic mutations. Of these, 22,910 were somatic substitutions, including 134 in exons (gene coding regions). One reviewer put their findings in perspective by estimating that "the number of mutations found suggests that a typical smoker would acquire one mutation for every 15 cigarettes smoked'.
It is well accepted that cancer can be propagated by multiple DNA mutations that are acquired via hereditary and natural means. The gene mutations can result in altered cellular homeostasis and confer growth and proliferative advantages. In turn, the collection of proteins that are involved in regulating the cell cycle and DNA replication/topology are the frequent targets of anti-cancer drugs. According to the data by Pleasance et al., gene mutations are evident in gene transcription and repair pathways in both cell types. Thus, their findings will provide insight into gene mutation processes, cellular repair pathways, and new molecular targets for anticancer agents in lung and skin cancer.
Identifying the causative mutations among the large number of mutations found will be the next challenge to overcome. Furthermore, achieving a complete genetic sequence for each cancer patient would be expected to help improve cancer treatment by helping doctors to select between different treatment options and individualizing patient care.References:
Pleasance ED et al. (2009) A small-cell lung cancer genome with complex signatures of tobacco exposure. Nature Available online at doi: 10.1038/nature08629
Pleasance ED, Cheetham RK et al. (2009) A comprehensive catalogue of somatic mutations from a human cancer genome. Nature Available online at doi: 10.1038/nature08658