Somatic Mutations and Ancestry Markers in Hispanic Lung Cancer Patients.

INTRODUCTION: To address the lack of genomic data from Hispanic/Latino (H/L) patients with lung cancer, the Latino Lung Cancer Registry was established to collect patient data and biospecimens from H/L patients. METHODS: This retrospective observational study examined lung cancer tumor samples from 163 H/L patients, and tumor-derived DNA was subjected to targeted-exome sequencing (>1000 genes, including EGFR, KRAS, serine/threonine kinase 11 gene [STK11], and tumor protein p53 gene [TP53]) and ancestry analysis. Mutation frequencies in this H/L cohort were compared with those in a similar cohort of non-Hispanic white (NHW) patients and correlated with ancestry, sex, smoking status, and tumor histologic type. RESULTS: Of the adenocarcinomas in the H/L cohort (n = 120), 31% had EGFR mutations, versus 17% in the NHW control group (p < 0.001). KRAS (20% versus 38% [p = 0.002]) and STK11 (8% versus 16% [p = 0.065]) mutations occurred at lower frequency, and mutations in TP53 occurred at similar frequency (46% versus 40% [p = 0.355]) in H/L and NHW patients, respectively. Within the Hispanic cohort, ancestry influenced the rate of TP53 mutations (p = 0.009) and may have influenced the rate of EGFR, KRAS, and STK11 mutations. CONCLUSIONS: Driver mutations in H/L patients with lung adenocarcinoma differ in frequency from those in NHW patients associated with their indigenous American ancestry. The spectrum of driver mutations needs to be further assessed in the H/L population.

Early2 factor (E2F) deregulation is a prognostic and predictive biomarker in lung adenocarcinoma.

Clinicians routinely prescribe adjuvant chemotherapy (ACT) for resected non-small cell lung cancer patients. However, ACT only improves five-year disease-free survival in stage I-III non-small cell lung cancer by 5-15%, with most patients deriving no benefit. Herein, deregulation of the E2F pathway was explored as a biomarker in lung adenocarcinoma patients. An E2F pathway scoring system, based on 74 E2F-regulated genes, was trained for RNA from two platforms: fresh-frozen (FF) or formalin-fixed paraffin-embedded (FFPE) tissues. The E2F score was tested as a prognostic biomarker in five FF-based cohorts and two FFPE-based cohorts. The E2F score was tested as a predictive biomarker in two randomized clinical trials; JBR10 and the NATCH (Neo-Adjuvant Taxol-Carboplatin Hope) trial. The E2F score was prognostic in untreated patients in all seven datasets examined (p < 0.05). Stage-specific analysis of combined cohorts demonstrated that the E2F score was prognostic in stage I patients (p = 0.0495 to <0.001; hazard ratio, HR, =2.04- 2.22) with a similar trend in other stages. The E2F score was strongly predictive in stage II patients from the two combined randomized clinical trials with a significant differential treatment effect (p = 0.015). Specifically, ACT improved survival in stage II patients with high E2F (p = 0.01; HR= 0.21). The 5-year survival increased from 18% to 81%. In contrast, in patients with low E2F, 5-year survival was 57% in untreated patients and 41% in ACT-treated patients with a HR of 1.55 (p = 0.47). In summary, the E2F score provides valuable prognostic information for Stage I and predictive information for Stage II lung adenocarcinoma patients and should be further explored as a decision support tool for their treatment.