Frequent activating STAT3 mutations and novel recurrent genomic abnormalities detected in breast implant-associated anaplastic large cell lymphoma

Piers Blombery; Ella Thompson; Georgina L Ryland; Rachel Joyce; David J Byrne; Christine Khoo; Stephen Lade; Mark Hertzberg; Greg Hapgood; Paula Marlton; Anand Deva; Geoffrey Lindeman; Stephen Fox; David Westerman; Miles Prince

doi:10.18632/oncotarget.26308

Frequent activating STAT3 mutations and novel recurrent genomic abnormalities detected in breast implant-associated anaplastic large cell lymphoma

Oncotarget. 2018 Nov 16;9(90):36126-36136. doi: 10.18632/oncotarget.26308.

Authors

Piers Blombery^{1

2}, Ella Thompson^{1

2}, Georgina L Ryland¹, Rachel Joyce^{3

4}, David J Byrne¹, Christine Khoo¹, Stephen Lade¹, Mark Hertzberg⁵, Greg Hapgood⁶, Paula Marlton⁶, Anand Deva⁷, Geoffrey Lindeman^{1

3

8}, Stephen Fox^{1

2}, David Westerman^{1

2}, Miles Prince^{1

2}

Affiliations

¹ Department of Pathology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
² Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC, Australia.
³ Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.
⁴ Department of Medical Biology, The University of Melbourne, Parkville, VIC, Australia.
⁵ Department of Haematology, Prince of Wales Hospital, University of New South Wales, Randwick, NSW, Australia.
⁶ Department of Haematology, Princess Alexandra Hospital, Brisbane, QLD, Australia.
⁷ Surgical Infection Research Group, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW, Australia.
⁸ Department of Medicine, The University of Melbourne, Parkville, VIC, Australia.

Abstract

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.

Keywords: NGS; genomics; lymphoma.