New Study Reveals Genomic Architecture of EGFR Mutations in Lung Cancer

WCLC 2015

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Becky Bunn
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New Study Reveals Genomic Architecture of EGFR Mutations in Lung Cancer

DENVER, Colo. – EGFR mutant (M+) is one of the most common driver oncogenes in lung cancer, typified by high response rates when treated with a tyrosine kinase inhibitor (TKI), and median progression free survival of 10 months, commonly due to emergence of T790M. The genomic architecture and spectra of EGFR M+ tumors may provide insights to mechanisms of treatment failure and no previous study describes this well.

Dr. Daniel SW Tan, Consultant, Medical Oncology, National Cancer Centre Singapore and Clinician Scientist Fellow at the Genome Institute of Singapore, presented his group’s finding today at a press briefing at the 16th World Conference on Lung Cancer (WCLC) hosted by the International Association of the Study of Lung Cancer (IASLC).

His team undertook a study performing whole exome and RNA-sequencing to determine genomic architecture of treatment naïve EGFR mutant lung cancers, (N=9, 47 sectors), as well as to elucidate mechanisms of resistance from analysis from a series TKI resistant biopsies.

“As emerging data implicate tumor evolution in drug resistance, we sought to gain insights into the mechanisms of clonal selection in EGFR mutant NSCLC, in order to develop strategies to overcome early treatment failure,” he said. 

He found that EGFR mutations consistently occur in trunks and that these tumors generally had a low-mutation burden across the exome (median 48, Range 9-98). The team also observed short trunks and high clonal diversity amongst East Asian lung cancer patients. Trunk mutations are found across all regions of a particular tumor, whereas private or branch mutations are found only in certain parts of the tumor.

Multiregion sequencing further identified co-existing driver trunk alterations as a possible mechanism for primary resistance in EGFR TKI, which is seen in 10-20 percent of patients with activating EGFR mutations.

Finally, sequencing TKI resistant samples highlight a subgroup of tumors with a high mutation burden, associated with a history of smoking.  “It is likely that additional subgroups within T790M positive and negative patients such as those with high mutation burden, will further emerge, and may form the basis for novel therapeutic approaches including immunotherapy,” he said.


About the WCLC:

The WCLC is the world’s largest meeting dedicated to lung cancer and other thoracic malignancies, attracting more than 7,000 researchers, physicians and specialists from more than 100 countries. The conference goal is to increase awareness and collaboration so that the latest developments in lung cancer can be understood and implemented throughout the world. Falling under the theme of “Fighting Lung Cancer,” the conference will cover a wide range of disciplines and unveil several research studies and clinical trial results. For the first time, IASLC has invited survivors to attend the conference free of charge. For more information on the 2015 WCLC, visit:

About the IASLC:

The International Association for the Study of Lung Cancer (IASLC) is the only global organization specifically dedicated to the study of lung cancer. Founded in 1974, the association's membership includes nearly 4,000 lung cancer specialists in 80 countries. For more information, visit:




September 9, 2015