Cancer can prove one of the nastiest diseases to crop up in one’s body due to it remaining hidden until it has already metastasized and spread around the system. A Baltimore/Boston collaboration of researchers set out to prove over half of the somatic mutations that make up a tumor are present before “tumor growth” of self-renewing tissues even starts.
Tumors form as the result of genetic mutations in which more cell replication and division happens than cell death. This causes the overgrowth of cells resulting in cancerous masses. Cancers aren’t caused by a single mutation, however. Many things must go wrong in cells before they get out of control. The basis of this study was to see how many passenger mutations (those that do not affect cell growth) actually occur before the tumor is initiated (by driver mutations) and whether or not this was affected by patient age.
To test, data was analyzed from The Cancer Genome Atlas and the International Cancer Genome Consortium of 676 patients with chronic lymphocytic lekemia (CLL), uterine corpus endometrioid carcinoma, colorectal cancer, or pancreatic cancer. The researchers first found that the total number of somatic mutations found in these cancers increased with patient age (at diagnosis) (P<0.01). The mutation to age correlation was independent of cancer stage.
The results further indicated that over 50% of passenger mutations developed before a single driver mutation in median aged patients. Using the regression data shown in the article, the number of somatic mutations at the earliest stage of cancer detection (after 25 years for colorectal, after 7 years for leukemia, and after 10 years for uterine) was estimated as 5.86, 33.3, and 50.2 in the different cancers. This suggested 68%, 57%, and 51% respectively of the somatic mutations happened before the tumors initiated.
Finally, the mutations rates were estimated, but did not deviate much from that of normal cells and bacteria.
The results from this study showing that the number of somatic mutations in a patient are age dependent and that a large number of these mutations appear before cancer growth begins are relevant for current genome-cancer studies. From this data, it may be possible to predict a cancer’s appearance before it even starts.
Catching cancer early is one of the most important keys to stopping it. This project is a step closer to faster cancer detection and elimination.
Cristian Tomasetti, Bert Vogelstein, Giovanni Parmigiani. Half or more of the somatic mutations in cancers of self-renewing tissues originate prior to tumor initiation. PNAS, 2013.