PTEN and cancer: Some of the new chromosomal rearrangements appearing exclusively in the metastases were found within known cancer genes such as PTEN, FHIT, and ESR1. For example, the patient P20 metastasis-acquired deletion of exons 5-7 in ESR1, which removes the ligand-binding domain, may result in an increased ER-signaling: both primary and metastasis were ER-positive; however PR, suggested as a surrogate marker for an activated ER-pathway [25], switched from negative in the primary to strongly positive in the metastasis.