Frequent activating STAT3 mutations and novel recurrent genomic abnormalities detected in breast implant-associated anaplastic large cell lymphoma.
Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a rare form of T-cell lymphoma that occurs after implantation of breast prostheses. We performed comprehensive next generation sequencing based genomic characterization of 11 cases of BIA-ALCL including sequence variant detection on 180 genes frequently mutated in haematological malignancy, genome-wide copy number assessment, structural variant detection involving the T-cell receptor loci and TRB deep-sequencing. We observed sequence variants leading to JAK/STAT activation in 10 out of 11 patients. We also observed germline TP53 mutations in two cases. In addition we detected a recurrent copy number loss involving RPL5 as well as copy number amplifications involving TNFRSF11A [RANK] (in 2 cases), MYC, P2RX7, TMEM119 and PDGFRA. In summary, our comprehensive genomic characterisation of 11 cases of BIA-ALCL has provided insight into potential pathobiological mechanisms (JAK/STAT, MYC and TP53) as well as identifying targets for future therapeutic intervention (TNFRSF11A, PDGFRA) in this rare entity.
['Blombery|Piers|P|', 'Thompson|Ella|E|', 'Ryland|Georgina L|GL|', 'Joyce|Rachel|R|', 'Byrne|David J|DJ|', 'Khoo|Christine|C|', 'Lade|Stephen|S|', 'Hertzberg|Mark|M|', 'Hapgood|Greg|G|', 'Marlton|Paula|P|', 'Deva|Anand|A|', 'Lindeman|Geoffrey|G|', 'Fox|Stephen|S|', 'Westerman|David|D|', 'Prince|Miles|M|']
genomics lymphoma NGS