TY - JOUR
T1 - Chromosome 20 loss is characteristic of breast implant-associated anaplastic large cell lymphoma
AU - Los-de Vries, G. Tjitske
AU - de Boer, Mintsje
AU - van Dijk, Erik
AU - Stathi, Phylicia
AU - Hijmering, Nathalie J.
AU - Roemer, Margaretha G. M.
AU - Mendeville, Matias
AU - Miedema, Daniel M.
AU - de Boer, Jan Paul
AU - Rakhorst, Hinne A.
AU - van Leeuwen, Flora E.
AU - van der Hulst, Rene R. W. J.
AU - Ylstra, Bauke
AU - de Jong, Daphne
N1 - Funding Information:
This work was supported by Dutch Cancer Society grants KWF 2015-7925, KWF 2015-7882, and KWF 2012-5711.
Publisher Copyright:
© 2020 by The American Society of Hematology.
PY - 2020/12/17
Y1 - 2020/12/17
N2 - Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a very rare type of T-cell lymphoma that is uniquely caused by a single environmental stimulus. Here, we present a comprehensive genetic analysis of a relatively large series of BIA-ALCL (n = 29), for which genome-wide chromosomal copy number aberrations (CNAs) and mutational profiles for a subset (n = 7) were determined. For comparison, CNAs for anaplastic lymphoma kinase (ALK)(-) nodal anaplastic large cell lymphomas (ALCLs; n = 24) were obtained. CNAs were detected in 94% of BIA-ALCLs, with losses at chromosome 20q13.13 in 66% of the samples. Loss of 20q13.13 is characteristic of BIA-ALCL compared with other classes of ALCL, such as primary cutaneous ALCL and systemic type ALK(+) and ALK(-) ALCL. Mutational patterns confirm that the interleukin-6-JAK1-STAT3 pathway is deregulated. Although this is commonly observed across various types of T-cell lymphomas, the extent of deregulation is significantly higher in BIA-ALCL, as indicated by phosphorylated STAT3 immunohistochemistry. The characteristic loss of chromosome 20 in BIA-ALCL provides further justification to recognize BIA-ALCL as a separate disease entity. Moreover, CNA analysis may serve as a parameter for future diagnostic assays for women with breast implants to distinguish seroma caused by BIA-ALCL from other causes of seroma accumulation, such as infection or trauma.
AB - Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a very rare type of T-cell lymphoma that is uniquely caused by a single environmental stimulus. Here, we present a comprehensive genetic analysis of a relatively large series of BIA-ALCL (n = 29), for which genome-wide chromosomal copy number aberrations (CNAs) and mutational profiles for a subset (n = 7) were determined. For comparison, CNAs for anaplastic lymphoma kinase (ALK)(-) nodal anaplastic large cell lymphomas (ALCLs; n = 24) were obtained. CNAs were detected in 94% of BIA-ALCLs, with losses at chromosome 20q13.13 in 66% of the samples. Loss of 20q13.13 is characteristic of BIA-ALCL compared with other classes of ALCL, such as primary cutaneous ALCL and systemic type ALK(+) and ALK(-) ALCL. Mutational patterns confirm that the interleukin-6-JAK1-STAT3 pathway is deregulated. Although this is commonly observed across various types of T-cell lymphomas, the extent of deregulation is significantly higher in BIA-ALCL, as indicated by phosphorylated STAT3 immunohistochemistry. The characteristic loss of chromosome 20 in BIA-ALCL provides further justification to recognize BIA-ALCL as a separate disease entity. Moreover, CNA analysis may serve as a parameter for future diagnostic assays for women with breast implants to distinguish seroma caused by BIA-ALCL from other causes of seroma accumulation, such as infection or trauma.
KW - MUTATIONS
KW - GENETICS
U2 - 10.1182/blood.2020005372
DO - 10.1182/blood.2020005372
M3 - Article
C2 - 33331925
SN - 0006-4971
VL - 136
SP - 2927
EP - 2932
JO - Blood
JF - Blood
IS - 25
ER -