Recurrent PTPRT/JAK2 mutations in lung adenocarcinoma among African Americans

Abstract

Reducing or eliminating persistent disparities in lung cancer incidence and survival has been challenging because our current understanding of lung cancer biology is derived primarily from populations of European descent. Here we show results from a targeted sequencing panel using NCI-MD Case Control Study patient samples and reveal a significantly higher prevalence of PTPRT and JAK2 mutations in lung adenocarcinomas among African Americans compared with European Americans. This increase in mutation frequency was validated with independent WES data from the NCI-MD Case Control Study and TCGA. We find that patients carrying these mutations have a concomitant increase in IL-6/STAT3 signaling and miR-21 expression. Together, these findings suggest the identification of these potentially actionable mutations could have clinical significance for targeted therapy and the enrollment of minority populations in clinical trials.

Whole-Exome Profiling of NSCLC Among African Americans

“…1B) and Supplementary Table 6). Again, this observation was validated in our previous data set based on targeted sequencing 5 and in TCGA (Table 2 and Fig. 1B).…”

“…1B, Table 2, and Supplementary Table 6). This increased mutation frequency was replicated in another data set 5 and in TCGA (Fig. 1B) and Supplementary Table 6).…”

“…2 In recent years, several large-scale genomic studies have begun to map differences in tumor biology between EAs and AAs. [4][5][6][7][8][9] These studies reveal that although most tumor biology is shared between EAs and AAs, specific and potentially actionable differences exist.…”

“…10 In recent years, studies using targeted exome sequencing approaches to analyze AA populations have been published. These studies reveal that much of the somatic mutation landscape of NSCLC is shared between EAs and AAs, 5,8,9 but also that some notable differences can be found, especially in lung adenocarcinoma (LUAD), including JAK2 and PTPRT. 5 Despite these observations, such ancestry differences in NSCLC genomics have yet to be systematically evaluated with whole-exome sequencing (WES) in an AA cohort.…”

“…These studies reveal that much of the somatic mutation landscape of NSCLC is shared between EAs and AAs, 5,8,9 but also that some notable differences can be found, especially in lung adenocarcinoma (LUAD), including JAK2 and PTPRT. 5 Despite these observations, such ancestry differences in NSCLC genomics have yet to be systematically evaluated with whole-exome sequencing (WES) in an AA cohort. A recent study by Lusk et al, 9 conducted WES on a subset of lung tumors without known driver mutations, the results of which suggested that an unbiased WES assessment in an unselected sample set was warranted.…”