Targeted Massively Parallel Sequencing Study Indicates Similarity of Somatic Driver Mutations in NSCLC for African American vs European Ancestry
In a study reported in the Journal of Clinical Oncology, Araujo et al used targeted massively parallel sequencing to produce an in-depth molecular profile of non–small cell lung cancer (NSCLC) in African Americans. Comparison with findings in patients of European/white ancestry with NSCLC indicated a similar profile for somatic driver mutations.
Study Details
A custom panel was designed to cover coding regions of 81 NSCLC-related genes and 40 ancestry-informative markers, with clinical samples being sequenced on a massively parallel sequencing instrument. The study cohort consisted of 99 African American patients (61% male, 94% smokers), including 31 with squamous and 68 with nonsquamous cell carcinomas.
Identified Mutations
A total of 227 nonsilent variants in the coding sequences of the 81 selected genes were detected. Of the 81 genes, 51 were mutated in one or more patients. The most frequent mutated genes were TP53 (33 patients), LRP1B (19), KRAS (16), CSMD1 (14), KEAP1 (14), SMARCA4 (7), MLL2 (7), EYS (7), EGFR (6), APC (6), EPHA3 (6), NOTCH1 (6), and ROS1 (6). Mutations in LRP1B, KRAS, CSMD1, SMARCA4, and EGFR tended to occur in nonsquamous tumors, and mutations in KEAP1, MLL2, EYS, NFE2L2, and CDKN2A tended to occur in squamous tumors.
Frequency of Driver Mutations
Nonoverlapping classic driver alterations were found in 24 patients, including in KRAS in 16, EGFR in 5, PIK3CA in 1, and NRAS in 1; an additional patient had ALK translocation on fluorescent in situ hybridization. Comparison with 283 NSCLC samples from white patients from The Cancer Genome Atlas database indicated that there were no significant differences in the frequency of driver mutations for whites vs African Americans in KRAS (18% vs 16%, P = .760) or EGFR (6% vs 5%, P = 1.00) or for any driver mutations (32% vs 24%, P = .163). Analysis of the combined data sets showed no significant association of ethnicity with status of KRAS, EGFR, or any driver mutation.
Analysis of copy number alterations in African American patients identified amplifications in the 3q chromosome arm in squamous cell but not nonsquamous carcinomas, including PIK3CA, SOX2, and TP63 (adjusted P < .05 for each).
The investigators concluded: “Our data suggest that African American ancestry may not be significantly different from European/white background for the presence of somatic driver mutations in NSCLC. Furthermore, we demonstrated that using a comprehensive genotyping approach could identify numerous targetable alterations, with potential impact on therapeutic decisions.”
David P. Carbone, MD, PhD, of The Ohio State University Medical Center, is the corresponding author of the Journal of Clinical Oncology article.
The study was supported by a fellowship from the Conquer Cancer Foundation of the American Society of Clinical Oncology and grants from the National Institutes of Health, National Cancer Institute, and The Ohio State Cancer Center. For full disclosures of the study authors, visit jco.ascopubs.org.
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