Catherine Wu

Background: Lung adenocarcinoma (LUAD) is the most prevalent histologic subtype of non-small cell lung cancer (NSCLC) and exhibits considerable molecular heterogeneity. Among the most clinically significant driver alterations are mutations in EGFR and KRAS, both of which influence treatment selection and oncologic outcomes. The prevalence of these mutations varies by race, yet racial minority populations remain underrepresented in genomic studies. EGFR alterations are more frequently observed in Asian patients, while KRAS mutations predominate in non-Asian cohorts. This study aimed to characterize race-associated differences in driver mutation prevalence among Asian, Black, and White patients with LUAD. Methods: A retrospective secondary cohort analysis was performed using publicly available clinicogenomic data from the Lung Adenocarcinoma Met Organotropism cohort, accessed via cBioPortal, comprising 2653 tumor samples. Patients were stratified by self-reported race into Asian, Black, and White cohorts; cases with missing race data were denoted as either other or unknown. Mutation frequencies for EGFR, KRAS, and TP53 were extracted from OncoPrint cohort study views and compared descriptively across groups. Results: Distinct race-associated differences in driver mutation prevalence were observed. Asian patients exhibited the highest frequency of EGFR alterations (64%), compared with Black (41%) and White (28%) cohorts. In contrast, KRAS mutations were least prevalent in Asian patients (10%) and more frequent in White (33%) and Black (23%) cohorts, indicating an inverse distribution between Asian and non-Asian populations. TP53 mutation prevalence was similar in Asian (52%) and White (53%) cohorts but was notably higher in Black patients (65%). Conclusions: Asian patients with LUAD exhibit a distinct molecular profile characterized by EGFR predominance, with direct implications for eligibility for EGFR-targeted tyrosine kinase inhibitor therapy. Black patients may also benefit from EGFR-based targeted therapies, but lack of large genomic data on Black populations warrants further investigation. White cohorts display a KRAS-dominant mutation pattern, suggesting divergent tumorigenic pathways and the potential need for alternative therapeutic strategies. The elevated TP53 frequency in Black patients remains to be further characterized. These findings support integrating race-associated genomic profiling into precision oncology frameworks to improve treatment selection and reduce disparities in outcomes.

The current pair of highly-powered, preregistered studies estimate the associations between personality/temperament and youth psychopathology, and evaluate the generalizability of these associations across diverse populations and research designs. In Study 1, a multilevel meta-analysis of 147 studies (N = 46,369) quantified the associations between Five-Factor Model personality traits and internalizing/externalizing psychopathology dimensions among subjects aged 1.5 to 18. All traits but openness evidenced small-to-medium bivariate associations with both psychopathology dimensions (z = |.18 - .46|). After adjusting for the covariance between internalizing and externalizing, each dimension showed a distinct personality profile. Internalizing was associated with neuroticism (β = .42) and negative-extraversion (β = -.37). Externalizing was associated with extraversion (β = .30), negative-conscientiousness (β = -.46), and negative-agreeableness (β = -.50). Most variance was driven by informant effects, particularly within the externalizing dimension and when personality and psychopathology were informed by the same person (i.e., mono-informant). Study 2 was a preregistered replication and extension of Study 1 in a large cohort of youth (N = 10,414) using individual-participant, item-level data. Most of Study 1’s associations were replicated for higher-order scales (e.g., Effortful Control) and for their lower-order scales (e.g., Activation Control). Again, mono-informant effects were more pronounced than cross-informant effects. Taken together, these studies provide the first quantitative synthesis of associations between personality/temperament and psychopathology in youth. These preregistered quantitative findings are largely consistent with decades of theory (e.g., Tackett, 2006), evidence a robustness of effects across populations, and highlight the impact of mono-informant effects.