Genome Study Charts Genetic Landscape of Lung Cancer

An international team of scientists today announced the results of a systematic effort to map the genetic changes underlying lung cancer, the world’s leading cause of cancer deaths. Appearing in the November 4 advance online issue of the journal Nature, the research provides a comprehensive view of the abnormal genetic landscape in lung cancer cells, revealing more than 50 genomic regions that are frequently gained or lost in human lung tumors. While one-third of these regions contain genes already known to play important roles in lung cancer, the majority harbor new genes yet to be discovered. Flowing from this work, the scientists uncovered a critical gene alteration — not previously linked to any form of cancer — that is implicated in a significant fraction of lung cancer cases, shedding light on the biological basis of the disease and a potential new target for therapy.

“This view of the lung cancer genome is unprecedented, both in its breadth and depth,” said senior author Matthew Meyerson, a senior associate member of the Broad Institute of MIT and Harvard and an associate professor at Dana-Farber Cancer Institute and Harvard Medical School. “It lays an essential foundation, and has already pinpointed an important gene that controls the growth of lung cells. This information offers crucial inroads to the biology of lung cancer and will help shape new strategies for cancer diagnosis and therapy.”

“The genomic landscape of lung cancer gives us a systematic picture of this terrible disease, confirming things we know, but also pointing us to many missing pieces of the puzzle,” said Eric Lander, one of the study’s co-authors and the founding director of the Broad Institute of MIT and Harvard. “More broadly, the study represents a general approach that can and should be used to analyze all types of cancer. Indeed, the study was designed as a pilot project for an even more comprehensive effort to unearth the genetic causes of cancer.”

Lung cancer is the leading cause of cancer deaths worldwide — each year more than 1 million people die of the disease, including more than 150,000 in the United States. New approaches to treatment rely on a deeper understanding of what goes wrong in cells to spur cancer growth. Through decades of research, it has become clear that lung cancer — like most human cancers — stems mainly from DNA changes that accrue in cells throughout a person’s life. But the nature of these changes and their biological consequences remain largely unknown.

To assemble a genome-wide catalog of genetic differences in lung cancer cells, a large-scale project was recently launched in lung adenocarcinoma. The effort, known as the Tumor Sequencing Project (TSP), unites scientists and clinicians throughout the cancer research community.

The TSP researchers studied more than 500 tumor specimens from lung cancer patients. Access to this large collection of high-quality samples made it possible to determine the genetic changes shared among different patients — such recurring changes can highlight important genes involved in cancer growth. “This project was made possible through the foresight of a dedicated group of oncologists, pathologists, and surgeons, who carefully and diligently preserved tissues from lung cancer patients over many years,” said Meyerson.