In the new study, the TSP team purified DNA from tumor samples and matching non-cancerous tissue donated by 188 patients with lung adenocarcinoma. Next, they sequenced the DNA to look for mutations in 623 genes with known or potential relationships to cancer. Prior to the study, fewer than a dozen genes had been implicated in lung adenocarcinoma. The latest research identified 26 new genes that are mutated in a significant number of samples. Most of these genes had not previously been associated with lung adenocarcinoma.

Among the genes newly implicated in lung adenocarcinoma are:


* Neurofibromatosis 1 (NF1). Mutations in this gene have previously been shown to cause neurofibromatosis 1, a rare inherited disorder characterized by unchecked growth of tissue of the nervous system.
* Ataxia Telengiectasia Mutated (ATM). ATM mutations have previously been shown to play a role in ataxia telangiectasia, which is a rare inherited neurological disorder of childhood, and in various types of leukemia and lymphoma.
* Retinoblastoma 1 (RB1). Past research has tied RB1 mutations to retinoblastoma, a relatively uncommon type of childhood cancer that originates in the eye's retina.
* Adenomatosis polyposis coli (APC). Mutations of this gene are common in colon cancer.
* Ephrin receptors A3 and A5 (EPHA3 and EPHA5), neurotrophin receptors (NTRK1 and NTRK3) and other receptor-coupled tyrosine kinases (ERBB4, KDR and FGFR4). These genes code for cell receptors coupled to members of the tyrosine kinase family of enzymes, which are considered prime targets for new cancer therapies.

After identifying the genetic mutations, the team went on to examine their impacts on biological pathways and determine which of those pathways were most crucial in lung adenocarcinoma. Such research is essential to efforts to develop new and better treatments for cancer.

For example, TSP researchers found more than two-thirds of the 188 tumors studied had at least one gene mutation affecting the mitogen-activated protein kinase (MAPK) pathway, indicating it plays a pivotal role in lung cancer. Based on those findings, the researchers suggested new treatment strategies for some subtypes of lung adenocarcinoma might include compounds that affect the MAPK pathway. One such group of compounds, called MEK inhibitors, has produced promising results in mouse models of colon cancer.

Likewise, the TSP's finding that more than 30 percent of tumors had mutations affecting the mammalian target of rapamycin (mTOR) pathway raises the possibility that the drug rapamycin might be tested in lung adenocarcinoma. Rapamycin is an mTOR-inhibiting compound approved for use in organ transplants and renal cancer.

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