Nikolaos Sousos, Máire Ní Leathlobhair, Christina Simoglou Karali, Eleni Louka, Nicola Bienz, Daniel Royston, Sally-Ann Clark, Angela Hamblin, Kieran Howard, Vikram Mathews, Biju George, Anindita Roy, Bethan Psaila, David C Wedge, Adam J Mead
The latency between acquisition of an initiating somatic driver mutation by a single-cell and clinical presentation with cancer is largely unknown. We describe a remarkable case of monozygotic twins presenting with CALR mutation-positive myeloproliferative neoplasms (MPNs) (aged 37 and 38 years), with a clinical phenotype of primary myelofibrosis. The CALR mutation was absent in T cells and dermal fibroblasts, confirming somatic acquisition. Whole-genome sequencing lineage tracing revealed a common clonal origin of the CALR-mutant MPN clone, which occurred in utero followed by twin-to-twin transplacental transmission and subsequent similar disease latency...
June 2022: Nature Medicine