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

Research output: Contribution to journalArticleResearchpeer-review

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.

LanguageEnglish
Pages36126-36136
Number of pages11
JournalOncotarget
Volume9
Issue number90
DOIs
Publication statusPublished - 1 Nov 2018

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Anaplastic Large-Cell Lymphoma
Breast Implants
Mutation
Breast Implantation
High-Throughput Nucleotide Sequencing
Germ-Line Mutation
T-Cell Lymphoma
Hematologic Neoplasms
T-Cell Antigen Receptor
Genome
Genes
Therapeutics

Bibliographical note

Copyright the Author(s). Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Keywords

  • Genomics
  • Lymphoma
  • NGS

Cite this

Blombery, Piers ; Thompson, Ella ; Ryland, Georgina L. ; Joyce, Rachel ; Byrne, David J. ; Khoo, Christine ; Lade, Stephen ; Hertzberg, Mark ; Hapgood, Greg ; Marlton, Paula ; Deva, Anand ; Lindeman, Geoffrey ; Fox, Stephen ; Westerman, David ; Prince, Miles. / Frequent activating STAT3 mutations and novel recurrent genomic abnormalities detected in breast implant-associated anaplastic large cell lymphoma. In: Oncotarget. 2018 ; Vol. 9, No. 90. pp. 36126-36136.
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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.",
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Blombery, P, Thompson, E, Ryland, GL, Joyce, R, Byrne, DJ, Khoo, C, Lade, S, Hertzberg, M, Hapgood, G, Marlton, P, Deva, A, Lindeman, G, Fox, S, Westerman, D & Prince, M 2018, 'Frequent activating STAT3 mutations and novel recurrent genomic abnormalities detected in breast implant-associated anaplastic large cell lymphoma' Oncotarget, vol. 9, no. 90, pp. 36126-36136. https://doi.org/10.18632/oncotarget.26308

Frequent activating STAT3 mutations and novel recurrent genomic abnormalities detected in breast implant-associated anaplastic large cell lymphoma. / Blombery, Piers; Thompson, Ella; Ryland, Georgina L.; Joyce, Rachel; Byrne, David J.; Khoo, Christine; Lade, Stephen; Hertzberg, Mark; Hapgood, Greg; Marlton, Paula; Deva, Anand; Lindeman, Geoffrey; Fox, Stephen; Westerman, David; Prince, Miles.

In: Oncotarget, Vol. 9, No. 90, 01.11.2018, p. 36126-36136.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Frequent activating STAT3 mutations and novel recurrent genomic abnormalities detected in breast implant-associated anaplastic large cell lymphoma

AU - Blombery,Piers

AU - Thompson,Ella

AU - Ryland,Georgina L.

AU - Joyce,Rachel

AU - Byrne,David J.

AU - Khoo,Christine

AU - Lade,Stephen

AU - Hertzberg,Mark

AU - Hapgood,Greg

AU - Marlton,Paula

AU - Deva,Anand

AU - Lindeman,Geoffrey

AU - Fox,Stephen

AU - Westerman,David

AU - Prince,Miles

N1 - Copyright the Author(s). Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

PY - 2018/11/1

Y1 - 2018/11/1

N2 - 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.

AB - 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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