Recurrent PTPRT/JAK2 mutations in lung adenocarcinoma among African Americans

非裔美国人肺腺癌中复发性 PTPRT/JAK2 突变

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作者:Khadijah A Mitchell, Noah Nichols, Wei Tang, Jennifer Walling, Holly Stevenson, Marbin Pineda, Roxana Stefanescu, Daniel C Edelman, Andrew T Girvin, Adriana Zingone, Sanju Sinha, Elise Bowman, Emily L Rossi, Rony F Arauz, Yuelin Jack Zhu, Justin Lack, Elizabeth Weingartner, Joshua J Waterfall, Sharo

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.

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