Recurrent PTPRT/JAK2 mutations in lung adenocarcinoma among African Americans

Author:

Mitchell Khadijah A.ORCID,Nichols NoahORCID,Tang WeiORCID,Walling JenniferORCID,Stevenson HollyORCID,Pineda Marbin,Stefanescu Roxana,Edelman Daniel C.,Girvin Andrew T.,Zingone Adriana,Sinha Sanju,Bowman Elise,Rossi Emily L.,Arauz Rony F.ORCID,Jack Zhu Yuelin,Lack Justin,Weingartner Elizabeth,Waterfall Joshua J.ORCID,Pine Sharon R.ORCID,Simmons John,Meltzer Paul,Ryan Bríd M.ORCID

Abstract

AbstractReducing 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.

Publisher

Springer Science and Business Media LLC

Subject

General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry

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