A Novel Channelopathy in Pulmonary Arterial Hypertension

n engl j med 369;22 nejm.org november 28, 2013 2161 mas. This combination is suggestive of chromothripsis, a single genetic event that results in focal losses and rearrangements in multiple genomic regions. Chromothripsis was previously described as being associated with aggressive forms of some types of cancer. The phenomenon of chromothripsis is typically not detected by means of conventional cytogenetic methods, and it was first described in the context of next-generation sequencing.1 We also showed that two sequential chromothripsis-like events can occur in a single tumor-cell lineage, and we described data supporting a clonal relationship between separate leiomyomas occurring in the same patient. We shed light on target genes with deletions on 7q and showed up-regulation of the key leiomyoma gene RAD51B in MED12-mutated leiomyomas. Although these findings cannot be interpreted from the data described by Markowski et al., their study is nonetheless a substantive contribution to a better understanding of the pathogenesis of leiomyomas.