The finding has been made possible through the collaboration of the cream of U.S. research. Washington, Houston, Massachusetts, Boston, New York, Michigan … The main laboratories in the country, with funding from the National Human Genome Research (NHGRI, according to its acronym in English), have joined together to decipher the genetic map of adenocarcinoma, the most common lung tumor.
For its work, the team led by Richard Wilson (University of Washington) used samples of tumor tissue from 188 patients. In total, the researchers sequenced more than 600 genes that so far had shown to be involved to a greater or lesser extent in the origin of cancer.
Using the latest genomic technology and multidisciplinary collaboration among nearly 100 specialists from different branches of science, this study has identified two years in just 26 genes that are highly mutated in adenocarcinoma cells but not healthy ones.
Some ‘unknown’ for oncologists
this figure almost triples the number of lung cancer genes known so far, it opens opportunities for future treatments. And what’s more, many of them never before been associated with this type of lung tumor.
“We were surprised especially NF1,” says Wilson elmundo.es. It is made of a gene linked to a rare disease called neurofibromatosis 1, as is ATM, another gene involved in a rare inherited disorder such as ataxia syndrome telengiectasia or Louis-Bar. Scientists also have discovered the relationship with lung cancer some genes related to other tumors, such as APC (implicated in cancer) or RB1 (retinoblastoma causing children).
However, the investigation has not been limited to detecting genes that are most frequently mutated in tumor cells than in normal, but has analyzed the relationships between them, looking for altered signaling pathways, incorrect connections and different patterns of mutations between smokers and nonsmokers. Not surprisingly, they recognize that patients with adenocarcinoma who were smoking accumulate in their cells about 50 mutations, while nonsmokers had just five ‘mistakes’.
Connections and signal paths
In other cases, the authors found that tumor cells that contained errors in genes such as EGFR or PTEN, tended to have lower rates of other mutations accumulated, which could indicate that they have greater ability to promote tumor growth alone, without need for other errors accumulate in DNA. For KRAS, another old acquaintance, for example, scientists found no relationship between their presence and grade of the tumor, which could indicate that this gene is especially critical in the initiation of carcinogenesis.
These findings tend to confirm that cancer is the result of an accumulation of genetic errors in our DNA (“no single magic gene,” says Wilson), loses its ability to repair as tumor cells acquire more and more mistakes. In fact, the study found that patients with more advanced cancer accumulate more mutations in their DNA than those with early stage disease.
In quantitative terms, in addition, some mutations were more frequently in 188 patients. This is the case of the MAPK pathway, which was observed in 70% of tumors; against mTOR, a mutation detected in 30% of the samples and opens the possibility that these tumors respond to treatment with rapamycin, a drug acting on this pathway and are already used to prevent rejection after organ transplantation.
“We have long known that cancer is a disease of a single gene,” says Dr. Wilson. “It is complex and can vary somewhat from one patient to another. We need to study more tumors and better understand their genome to better understands all the possible combinations of mutations that cause and our study represents a major advance in this direction,” he stresses.
Despite the giant step that this paper represents the authors acknowledge that even tumors will require larger samples and further work to continue to understand the complexity and molecular genetics of lung cancer. “This pioneering study has allowed us to obtain clearer and more complete portrait of this disease has been achieved to date. This ‘picture’ will allow us to focus our research efforts from now on and accelerate efforts to develop new strategies to disarm this devastating evil. ”