Sequencing the human genome in cancer and leukemia
Scientists at Washington University in St Louis have decoded the genes of a woman who had acute myeloid leukemia (AML) and discovered a set of mutations that may have caused the disease or aided it's progression, according to an article published today in Nature.
Washington University (who also provided the photo on the right of the leukemia cells), also noted in their press release:
tumor DNA that appeared to be relevant to her disease; eight of the
mutations were rare and occurred in genes that had never been linked to
AML. They also showed that virtually every cell in the tumor sample had
nine of the mutations, and that the single genetic alteration that
occurred less frequently was likely the last to be acquired. The
scientists suspect that all the mutations were important to the
patient's cancer."
What is the significance of this fascinating research? Well, this is the first time such sequencing has been done and may lay the foundation
for more comprehensive genome-wide studies of this nature in other
cancers.
Just two of the 10 mutations the researchers found had been linked to AML previously, so the other 8 were a new and fascinating find. They were able to do this by selecting cancer cells from the patients bone marrow and comparing them to normal, healthy skin cells. Being able to compare the patient's normal cells to the AML cells may allows scientists to start unlocking the hidden genetic
transformations and ultimately, design new therapies that target the
critical mutations.
Most work on cancer mutations has focused on a few hundred genes
already suspected of being involved in the disease, not the 20,000 or
so genes that make up the full human genome. In other words, how can you hit a target if you don't know what it is? Using this new approach, scientists can separate out which mutations are most relevant to that particular cancer patient and one day, we may be able to then determine which therapy would be most suitable for them based on the mutational analysis.
Clearly, identification of new mutations critically evolved in a cancer also means new targets for therapeutic intervention and design of new drugs based on inhibiting the specific gene or kinase, much in the way Gleevec targets the BCR-ABL gene in chronic myeloid leukemia (CML). If a similar approach could be designed for other cancers, then it is likely that more cost effective medications with fewer side effects may result in the long run. That's good news for patients.
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2 Responses to “Sequencing the human genome in cancer and leukemia”
Great post! 🙂
Cancer is a disease of genes gone awry, and new insights into the cancer genome could point the way to effective treatments. Looking at these set of genes could provide clues as to what is causing cancer and provide opportunities about developing therapeutic strategies against it.
If you take a 1,000 mutations in kinase genes alone which are putatively associated with cancer and try to figure out how many combinations of these mutations one could have, and then consider that mutations are only the beginning, because it depends on the factors which regulate those genes and how much the genes are expressed or repressed, and how all those things interact with all the other things which are going on, you have a pretty major challenge, if you want to build a model of the cancer cell from the bottom up.
Kinase genes are just the tip of the iceberg though. They are only a miniscule portion of the total cancer genome. The analysis over the long haul are moving away from the kinases into the rest of the genome. All of this bodes well for cancer medicine, which is becoming more tailored to the genetics of a particular patient and his/her particular tumor.
We can take a cancer specimen, analyze it, and follow those genetic changes that influence particular pathways. Then we use one, two, three or more targeted therapies, perhaps simultaneously, and try to completely interrupt the flow of the cancer process.
However, there are some who feel the properties of individual cancer cells are irrelevant to the cure or control of cancer. Cancer is about the properties of evolutionary populations of cells. That implies that the required target for the consistent and specific cure or control of cancer is the set of all malignant cells that could evolve. Targeting a lesser set will fail. It will act as a selective pressure that changes the course, but not the flow of tumor cell evolution.
One of the weaknesses of the existing organizational structure for cancer research is the reluctance to address multiple design features concurrently. Multi-dimensional problems require multi-dimensional solutions and coordinated team efforts.
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