Pathway alterations in LSCC fell into two major categories. Not surprisingly, the squamous differentiation pathway was altered in 44% of patients, but the oxidative stress response was also found to be altered in 34% of patients and 62% of those with the classical mRNA subtype. Three mutually exclusive mutations were lost within this pathway: KEAP1 in 12%, NFE2L2 in 19% and cullin 3 in 7%.
Citing the role of oxidative stress in chemotherapy resistance, Dr. Mitsudomi said, "This is really an important discovery."
Finally, Dr. Govindan said the lung cancer community is witnessing a revolution." We are at the dawn of a new era where we are going to study the cancer genomes in its entirety as we have never done before.
"We used to see the alterations in the cancer genes through a key hole and now we can actually have this panoramic view of this through this comprehensive approach."
The full paper on the TCGA Lung Cancer Project findings is expected to be published shortly and will be deposited in a public database, Dr. Govindan said.
Dr. Govindan reports a consulting or advisory role with Bayer, Boehringer Ingelheim, and Merck Serono. The Cancer Genome Atlas is supported by the National Institutes of Health. Dr. Mitsudomi reports a consulting/advisory role with Boehringer Ingelheim, Kyowa Hakko Kirin, Lilly, and Pfizer and honoraria from AstraZeneca, Chugai Pharma, Lilly, and Roche.