TY - JOUR
T1 - HIF2A Germline-Mutation-Induced Polycythemia in a Patient with VHL-Associated Renal-Cell Carcinoma
AU - Liu, Qiuli
AU - Tong, Dali
AU - Liu, Gaolei
AU - Yi, Yuting
AU - Zhang, Dianzheng
AU - Zhang, Jun
AU - Zhang, Yao
AU - Huang, Zaoming
AU - Li, Yaoming
AU - Chen, Rongrong
AU - Guan, Yanfang
AU - Yi, Xin
AU - Jiang, Jun
PY - 2017/12/2
Y1 - 2017/12/2
N2 - 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.
AB - 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.
KW - HIF2A
KW - VHL
KW - polycythemia
KW - renal carcinoma
UR - https://digitalcommons.pcom.edu/scholarly_papers/1894
M3 - Article
VL - 18
JO - Cancer Biology Therapy
JF - Cancer Biology Therapy
ER -