Research Papers:

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 and Miles Prince

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Oncotarget. 2018; 9:36126-36136. https://doi.org/10.18632/oncotarget.26308

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Piers Blombery1,2, Ella Thompson1,2, Georgina L. Ryland1, Rachel Joyce3,4, David J. Byrne1, Christine Khoo1, Stephen Lade1, Mark Hertzberg5, Greg Hapgood6, Paula Marlton6, Anand Deva7, Geoffrey Lindeman1,3,8, Stephen Fox1,2, David Westerman1,2 and Miles Prince1,2

1Department of Pathology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia

2Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC, Australia

3Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia

4Department of Medical Biology, The University of Melbourne, Parkville, VIC, Australia

5Department of Haematology, Prince of Wales Hospital, University of New South Wales, Randwick, NSW, Australia

6Department of Haematology, Princess Alexandra Hospital, Brisbane, QLD, Australia

7Surgical Infection Research Group, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW, Australia

8Department of Medicine, The University of Melbourne, Parkville, VIC, Australia

Correspondence to:

Piers Blombery, email: [email protected]

Keywords: lymphoma; genomics; NGS

Received: July 29, 2018     Accepted: October 25, 2018     Published: November 16, 2018


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.

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