Next generation sequencing of breast implant‐associated anaplastic large cell lymphomas reveals a novel STAT3‐JAK2 fusion among other activating genetic alterations within the JAK‐STAT pathway

• Published in: The breast journal Vol. 27; no. 4; pp. 314 - 321
• Main Authors: Quesada, Andrés E., Zhang, Yanming, Ptashkin, Ryan, Ho, Caleb, Horwitz, Steven, Benayed, Ryma, Dogan, Ahmet, Arcila, Maria E.
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.04.2021
• Subjects: Anaplastic large-cell lymphoma; Breast; breast implant associated anaplastic large cell lymphoma; Breast implants; Breast Implants - adverse effects; Breast Neoplasms - genetics; Female; fusions; Gastrointestinal system; Gastrointestinal tract; hematopathology; High-Throughput Nucleotide Sequencing; Humans; Immunoproliferative diseases; Janus kinase; Janus kinase 2; Janus Kinase 2 - genetics; Lymphocytes; Lymphoid tissue; Lymphoma; Lymphoma, Large-Cell, Anaplastic - genetics; Mutation; mutations; Next-generation sequencing; Revisions; Stat3 protein; STAT3 Transcription Factor - genetics; STAT3‐JAK2 fusion; structural rearrangements; Tumors; hematopathology; mutations; structural rearrangements; next generation sequencing; fusions; breast implant associated anaplastic large cell lymphoma; STAT3-JAK2 fusion
• ISSN: 1075-122X; 1524-4741
• DOI: 10.1111/tbj.14205

Breast implant associated anaplastic large cell lymphoma (BIA‐ALCL) is a distinct type of ALCL, and a new provisional entity by the 2016 revision of the World Health Organization (WHO) classification of tumors of hematopoietic and lymphoid tissues. In contrast to systemic and primary cutaneous ALCLs, BIA‐ALCLs have been genetically characterized by the absence of fusions and frequent activation of the JAK‐STAT3 pathway through mutations in JAK1 and STAT3. In this study, we report the results of the genetic profiling of 9 BIA‐ALCL cases supporting the role of the JAK‐STAT pathway activation in this entity, including the identification of an activating STAT3‐JAK2 fusion similar to those recently reported in T‐cell lymphoproliferative disorders of the gastrointestinal tract. To our knowledge, this is the first fusion reported in BIA‐ALCL, providing further insight into the overall genetic landscape of this rare entity as well as uncovering potential options for targeted therapy in cases with advanced disease.