Frequent Activating STAT3 Mutations and Novel Recurrent Genomic Abnormalities Detected in Breast Implant-associated Anaplastic Large Cell Lymphoma

Overview

Journal Oncotarget

Specialty Oncology

Date 2018 Dec 15

PMID 30546832

Citations 34

Authors

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

Affiliations

Soon will be listed here.

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 mutations in two cases. In addition we detected a recurrent copy number loss involving RPL5 as well as copy number amplifications involving [RANK] (in 2 cases), , , and . 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.

Citing Articles

BIA-ALCL and BIA-SCC: Updates on Clinical Features and Genetic Mutations for Latest Recommendations.

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PMID: 38792976 PMC: 11122735. DOI: 10.3390/medicina60050793.

Management of complications following implant-based breast reconstruction: a narrative review.

Meshkin D, Firriolo J, Karp N, Salibian A Ann Transl Med. 2024; 11(12):416.

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The implication of next-generation sequencing in the diagnosis and clinical management of non-Hodgkin lymphomas.

Tomacinschii V, Mosquera Orgueira A, Aliste Santos C, Robu M, Buruiana S, Fraga Rodriguez M Front Oncol. 2023; 13:1275327.

PMID: 38023160 PMC: 10663367. DOI: 10.3389/fonc.2023.1275327.

Malignant Neoplasms Arising in the Cardiac Pacemaker Cavity: A Systematic Review.

de Moraes F, Moro L, Pessoa F, Passos E, Campos R, Souza D Cancers (Basel). 2023; 15(21).

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CD30 Lateral Flow and Enzyme-Linked Immunosorbent Assays for Detection of BIA-ALCL: A Pilot Study.

Zeyl V, Xu H, Khan I, Machan J, Clemens M, Hu H Cancers (Basel). 2023; 15(21).

PMID: 37958303 PMC: 10649192. DOI: 10.3390/cancers15215128.

References

Feldman A, Dogan A, Smith D, Law M, Ansell S, Johnson S . Discovery of recurrent t(6;7)(p25.3;q32.3) translocations in ALK-negative anaplastic large cell lymphomas by massively parallel genomic sequencing. Blood. 2010; 117(3):915-9. PMC: 3035081. DOI: 10.1182/blood-2010-08-303305. View

Hofman I, van Duin M, De Bruyne E, Fancello L, Mulligan G, Geerdens E . RPL5 on 1p22.1 is recurrently deleted in multiple myeloma and its expression is linked to bortezomib response. Leukemia. 2016; 31(8):1706-1714. PMC: 5380219. DOI: 10.1038/leu.2016.370. View

Tan W, Zhang W, Strasner A, Grivennikov S, Cheng J, Hoffman R . Tumour-infiltrating regulatory T cells stimulate mammary cancer metastasis through RANKL-RANK signalling. Nature. 2011; 470(7335):548-53. PMC: 3166217. DOI: 10.1038/nature09707. View

Lee Y, Filie A, Arthur D, Fojo A, Jaffe E . Breast implant-associated anaplastic large cell lymphoma in a patient with Li-Fraumeni syndrome. Histopathology. 2015; 67(6):925-7. PMC: 4644504. DOI: 10.1111/his.12737. View

Bolotin D, Poslavsky S, Mitrophanov I, Shugay M, Mamedov I, Putintseva E . MiXCR: software for comprehensive adaptive immunity profiling. Nat Methods. 2015; 12(5):380-1. DOI: 10.1038/nmeth.3364. View

Di Napoli A, Jain P, Duranti E, Margolskee E, Arancio W, Facchetti F . Targeted next generation sequencing of breast implant-associated anaplastic large cell lymphoma reveals mutations in JAK/STAT signalling pathway genes, TP53 and DNMT3A. Br J Haematol. 2016; 180(5):741-744. DOI: 10.1111/bjh.14431. View

Swerdlow S, Campo E, Pileri S, Lee Harris N, Stein H, Siebert R . The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016; 127(20):2375-90. PMC: 4874220. DOI: 10.1182/blood-2016-01-643569. View

Fancello L, Kampen K, Hofman I, Verbeeck J, De Keersmaecker K . The ribosomal protein gene RPL5 is a haploinsufficient tumor suppressor in multiple cancer types. Oncotarget. 2017; 8(9):14462-14478. PMC: 5362418. DOI: 10.18632/oncotarget.14895. View

Blombery P, Thompson E, Jones K, Arnau G, Lade S, Markham J . Whole exome sequencing reveals activating JAK1 and STAT3 mutations in breast implant-associated anaplastic large cell lymphoma anaplastic large cell lymphoma. Haematologica. 2016; 101(9):e387-90. PMC: 5060038. DOI: 10.3324/haematol.2016.146118. View

10.

Gunawardana J, Chan F, Telenius A, Woolcock B, Kridel R, Tan K . Recurrent somatic mutations of PTPN1 in primary mediastinal B cell lymphoma and Hodgkin lymphoma. Nat Genet. 2014; 46(4):329-35. DOI: 10.1038/ng.2900. View

11.

Clemens M, Horwitz S . NCCN Consensus Guidelines for the Diagnosis and Management of Breast Implant-Associated Anaplastic Large Cell Lymphoma. Aesthet Surg J. 2017; 37(3):285-289. DOI: 10.1093/asj/sjw259. View

12.

Lipton A, Fizazi K, Stopeck A, Henry D, Brown J, Yardley D . Superiority of denosumab to zoledronic acid for prevention of skeletal-related events: a combined analysis of 3 pivotal, randomised, phase 3 trials. Eur J Cancer. 2012; 48(16):3082-92. DOI: 10.1016/j.ejca.2012.08.002. View

13.

Branstetter D, Nelson S, Manivel J, Blay J, Chawla S, Thomas D . Denosumab induces tumor reduction and bone formation in patients with giant-cell tumor of bone. Clin Cancer Res. 2012; 18(16):4415-24. DOI: 10.1158/1078-0432.CCR-12-0578. View

14.

Zebisch A, Lal R, Muller M, Lind K, Kashofer K, Girschikofsky M . Acute myeloid leukemia with TP53 germ line mutations. Blood. 2016; 128(18):2270-2272. PMC: 5095760. DOI: 10.1182/blood-2016-08-732610. View

15.

Laimer D, Dolznig H, Kollmann K, Vesely P, Schlederer M, Merkel O . PDGFR blockade is a rational and effective therapy for NPM-ALK-driven lymphomas. Nat Med. 2012; 18(11):1699-704. DOI: 10.1038/nm.2966. View

16.

Hu H, Johani K, Almatroudi A, Vickery K, Van Natta B, Kadin M . Bacterial Biofilm Infection Detected in Breast Implant-Associated Anaplastic Large-Cell Lymphoma. Plast Reconstr Surg. 2016; 137(6):1659-1669. DOI: 10.1097/PRS.0000000000002010. View

17.

Bougeard G, Limacher J, Martin C, Charbonnier F, Killian A, Delattre O . Detection of 11 germline inactivating TP53 mutations and absence of TP63 and HCHK2 mutations in 17 French families with Li-Fraumeni or Li-Fraumeni-like syndrome. J Med Genet. 2001; 38(4):253-7. PMC: 1734839. DOI: 10.1136/jmg.38.4.253. View

18.

Fata J, Kong Y, Li J, Sasaki T, Irie-Sasaki J, Moorehead R . The osteoclast differentiation factor osteoprotegerin-ligand is essential for mammary gland development. Cell. 2000; 103(1):41-50. DOI: 10.1016/s0092-8674(00)00103-3. View

19.

Shugay M, Bagaev D, Zvyagin I, Vroomans R, Crawford J, Dolton G . VDJdb: a curated database of T-cell receptor sequences with known antigen specificity. Nucleic Acids Res. 2017; 46(D1):D419-D427. PMC: 5753233. DOI: 10.1093/nar/gkx760. View

20.

Yoshimura A, Nishinakamura H, Matsumura Y, Hanada T . Negative regulation of cytokine signaling and immune responses by SOCS proteins. Arthritis Res Ther. 2005; 7(3):100-10. PMC: 1174965. DOI: 10.1186/ar1741. View