<i>PTEN</i> loss-of-function mutations occur in ~40% of BRAFV600E melanomas, resulting in increased PI3K/AKT activity that enhances resistance to BRAF/MEK combination inhibitor therapy.<h4>Methods</h4>To compare the response of <i>PTEN</i> null to <i>PTEN</i> wild-type cells in an isogenic background, CRISPR/Cas9 was used to knock out <i>PTEN</i> in a melanoma cell line that harbors a <i>BRAFV600E</i> mutation. The gene discussed is PTEN; the disease is melanoma.