Clickety clack, clickety clack, clickety clack, ping…… ziiip. Who has never experienced the unique metallic sounds of a manual typewriter? With the tick of each key on the keyboard the typewriter leaves permanent impressions of letters upon a sheet of paper. Clickety clack, clickety clack, clickety clack, ping… pshsht. The sound of the hauled sheet out of the typewriter anticipates the verdict. The evidence displays the flow of incorruptible thoughts and the ever-present typing slips and spelling errors. There are no ways to rectify the meaningless words and phrases; they are eternally engraved onto that piece of paper.
Whereas the repertoire of misspelled words produces titters of amusements, in contrast, the errors generated through the addition of incorrect DNA building blocks (nucleotides) during DNA replication (i.e., generation of near perfect copies of themselves) in cells lead to mutagenesis and possibly cancer. Within this cellular typewriter, the “typist”, so-called DNA polymerase, “spells out” the code imprinted on the template DNA and simultaneously adds one nucleotide at a time, matching those on the growing DNA strand. This ultimately generates a near precise impression of the template’s code on the newly synthesized strand. In contrast to a typist in a hurry who might simply X-out the typos, the little “spelling” imperfections of DNA replication are monitored and corrected by multiple and complex repair processes. Yet, even these flawless cellular “proofreaders and editors” miss out errors, and thus generate sequence alterations known as mutations. When you displace T for N your “Tasty” dish becomes strangely “Nasty”. Instead, the swapping of one nucleotide during DNA replication, such as TTC to TTA, introduces a premature stop signal causing any resulting protein to be shortened. These abnormally shortened products can have a damaging effect on cells and represent an underlying cause of cancer.
Now, scientists have catalogued the mutations that occur in 21 breast cancers through time, in essence mapping the cancers’ life history. They showed which mutations happened, how early or late the mutations were in the cancers life, and at what stage it would get diagnosed. They pinpointed five areas where mutations are likely to happen, giving us a detailed insight into the cancer’s world.
Typing and spelling mistakes helps out the clumsiest writers to detect and correct errors, the information on mutation variants presented in this study, may allow scientists to assess the type of cancer, what stage it is at, and ultimately determine the specific mode of action. This may well be the beginning for wide-ranging opportunities for personalized treatment of patients with cancer.
Nik-Zainal, S., et al., The life history of 21 breast cancers. Cell, 2012. 149(5): p. 994-1007.
Nik-Zainal, S., et al., Mutational processes molding the genomes of 21 breast cancers. Cell, 2012. 149(5): p. 979-93.