HIF2A Germline-Mutation-Induced Polycythemia in a Patient with VHL-Associated Renal-Cell Carcinoma

Document Type

Article

Publication Date

12-2-2017

Abstract

In this study, we report here a rare case of polycythemia and cRCC in the same patient, which may be helpful in understanding clinical features and molecular mechanisms underlying VHL-mutation-associated cRCC and polycythemia induced by germline mutation of HIF2A. Firstly, we identified a rare but well studied germline mutation resulting in polycythemia in HIF2A (c.1609G>A, p.Gly537Trp) in the blood of the patient and his daughter. Meanwhile, we identified an inactivating VHL mutation (c.391A>T, p.N131Y), as well as TP53 mutation(c.977A>T, p.E326V) and mTOR mutation(c.7498A>T, p.I2500F) in renal cancer tissue. Moreover, protein levels of VHL, HIF1A, HIF2A, EPO, and VEGF estimated by immunohistochemical staining substantiated hyperactivation of the oxygen-sensing pathway. In addition, we identified 158 somatic SNP/indel mutations, including 90 missense/nonsense/splice/stop-loss mutations by whole-exome sequencing (WES) of the tumor specimen and matched normal DNA.

Publication Title

Cancer Biology & Therapy

Volume

18

Issue

12

First Page

944

Last Page

947

PubMed ID

29172931

Comments

This article was published in Cancer Biology & Therapy, Volume 18, Issue 12, Pages 944-947.

The published version is available at http://dx.doi.org/10.1080/15384047.2017.1394553.

Copyright © 2017.

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