ALK translocations predominate
Dr. Kosuke Tanaka
In the second study, Dr. Kosuke Tanaka of the department of thoracic oncology at Aichi Cancer Center Hospital in Nagoya, Japan, performed retrospective genomic screening of 67 consecutive patients who received a diagnosis of lung adenocarcinoma when aged 40 years or younger.
All patients had evaluation for EGFR and KRAS mutations, and most had evaluation for ALK translocations. Those negative for all three had additional testing.
The patients had a median age of 36 years, 60% were female, and 68% had stage IV disease, Dr. Tanaka reported. The majority, 61%, were former or current smokers.
Overall, 82% of the patients were found to have targetable alterations of driver oncogenes. The most common were ALK translocation (seen in 45%) and EGFR mutation (27%); KRAS mutation was uncommon (3%). Among 15 patients known to be negative for all of these, analyses identified HER2 mutations in three and RET mutations in two.
Driver mutations were more common among patients who had no or only a light smoking history, compared with peers who smoked (89% vs. 72%, P = .069). ALK translocation was more common in patients with stage IV disease (58% vs. 18%, P = .002).
“Early-emerging adenocarcinoma has a very high possibility of having some targetable driver oncogenes,” Dr. Tanaka concluded. “Among younger populations, examination of all known oncogenes, including minor ones, is strongly recommended.”
Data finger genes involved in cell adhesion
In the third study, investigators performed genomic analysis in 20 patients from the Cleveland Clinic who underwent surgery for non–small-cell lung cancer (NSCLC) that was diagnosed at age 45 years or younger.
Dr. Patrick C. Ma
Overall, 60% were female and 65% had smoked at some time, reported lead author Dr. Patrick C. Ma of the Mary Babb Randolph Cancer Center at West Virginia University, Morgantown, and the Sun Yat-sen University Cancer Center’s State Key Laboratory of Oncology in South China and the Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
Some 55% of patients had adenocarcinomas, and 20% had stage IV disease. Of note, 25% had a history of some other type of cancer and 60% had a first-degree relative with a cancer diagnosis.
The somatic mutation rate was much higher in ever-smokers than never-smokers (3.47 vs. 0.76 per megabase). The former value “is a relatively high mutational burden, standing shoulder to shoulder with melanoma and bladder cancer,” Dr. Ma pointed out.
Mutations of key driver genes such as TP53 and KRAS were seen exclusively in smokers, but EGFR mutations were more often seen in never-smokers.
Further analyses indicated that genes involved in cell adhesion and epithelial-mesenchymal transition (EMT) showed a sevenfold enrichment in mutation frequency in the cohort, compared with that seen in the lung cancer data set of the Cancer Genome Atlas.
“Our study nominated novel candidate genes and pathways especially related to cell adhesion and EMT process that potentially may play a role in early-onset NSCLC, whether in smokers or nonsmokers,” Dr. Ma said.
“Further analysis and validation of our findings will improve our understanding of lung cancer pathogenesis, especially in younger patients, and eventually lead to precision therapies to benefit these younger patients,” he concluded.
Dr. Gitlitz disclosed that she is on the speakers bureaus of Genentech and Eli Lilly. Dr. Tanaka and Dr. Ma disclosed that they had no relevant conflicts of interest.