Abstract 514P
Background
Lung adenocarcinoma comprises a molecularly heterogeneous subtype of lung cancers, the characteristics of which vary widely based on age, sex, and ethnicity as well as factors such as smoking history. Certain subsets of the population affected by LUAD possess therapeutically actionable mutations. This study aims to determine the differences in the molecular landscape and survival characteristics in patients of varying ethnicity and age of disease onset.
Methods
We analyzed publicly available somatic mutation data from whole genome and whole exome sequencing of three cohorts of LUAD patients: the NCI Nature Genetics lung study, the OncoSG LUAD study, and the TCGA LUAD study. The cohorts were subsetted separately based on diagnosis age (<45 years vs. >60 years) and ethnic group (Asian vs. Not Hispanic or Latino) by creation of custom groups on cbioportal. Downstream analysis of genomic alterations and survival characteristics was done.
Results
Most frequently altered genes across age groups were TP53 and NAV3, LRP1B, NAV3, PHKG1, ESYT2 showing the most significantly higher prevalence in younger patients. Structural variants and CNA were greater in the younger group, EML4-ALK fusions being the most important. Log Rank Test p-value = 0.728 showed no significant survival difference based on age. Analysis based on ethnicity revealed that the most frequently altered genes were TP53, EGFR, and TTN; EGFR had a distinctively greater preponderance in the Asian cohort. EML4-ALK fusion was the most frequent among CNA and structural variants, which were greater in Asians. A median survival of 114.90 (85.27-NA) months was documented in Asian patients and 46.72 (41.36-53.65) months in the comparison group. Asians showed greater survival (log rank test p-value = 5.331e-6).
Conclusions
Young onset LUAD has a greater frequency of mutations, most commonly involving constitutively active tyrosine kinases. Greater CNA, as in MUC and KRTAP gene families, may also promote tumorigenesis in these individuals. EGFR mutations and structural variants (EML4-ALK) were found in greater frequency in Asians. Interestingly, Asians also showed a significant survival advantage, probably attributable to therapeutically actionable receptor tyrosine kinase mutations.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.