16th World Conference on Lung Cancer (WCLC) Presidential Symposium: Summary and Clinical Implications

Gilberto Lopes, MD, MBA


October 12, 2015

In This Article

Genomic Sequencing of EGFR-Mutated NSCLC

In the third study,[6] investigators from the National Cancer Center in Singapore presented the first thorough genomic analysis of naive and resistant patients with EGFR mutations. They sequenced the exome of 46 sectors (ranging from four to 11 sectors per tumor) from eight patients with resected NSCLC. There was a median of 52.5 mutations per tumor, ranging from 15 to 112, significantly fewer than what is seen in non-EGFR-mutated lung cancers. Primary EGFR mutations were truncal events in all cases, and the commonly seen resistance mutation T790M was notable for its absence, even at sequencing depths of 2000x. Between 10% and 33% of all mutations were private for each tumor and, at least for some, harbored potential drivers of subclonal diversity including p53, AKT1, and ATXN1. Of 30 tumors resistant to EGFR tyrosine kinase inhibitors, 16 harbored T790M mutations, and 14 did not. Exome sequencing revealed a higher mutation burden (median of 80 mutations per tumor), and SNP array and expression data confirmed HER2 and MET as common coexisting resistance mechanisms.

These findings provide us with a better understanding of the genomics of treatment-naive and -resistant patients with EGFR mutations.


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