Research Paper Volume 12, Issue 7 pp 5781—5791

A novel germline gain-of-function HIF2A mutation in hepatocellular carcinoma with polycythemia

Figure 2. Sanger sequencing, genetic pedigree, and localization of germline mutation in the index patient and family members. (A) Direct Sanger sequencing results are shown for the HIF2A gene in the index patient and affected family members. The patient’s blood lymphocytes as well as the tumor and surrounding liver tissue carried a G1645A mutation in the gene coding for HIF2A. This mutation was also present in the blood lymphocytes of two of the patient’s sisters and one niece. (B) A family pedigree is shown. (C) Sanger sequencing of the p53 gene in the tumor tissue and blood lymphocytes of the index patient is shown. The p53 mutation was present only in the index patient’s tumor tissue. (D) Multiple peptide sequence alignment was performed; the E549 site was critically conserved across species (arrow). As such, a mutation at this site could potentially alter HIF-2α signaling.