Search

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a subtype of T-cell lymphoma with much of its pathogenesis poorly understood. Mutations in the JAK/STAT pathway have been identified in a substantial proportion of cases, as well as copy number aberrations (CNAs). However, a more discrete characterization is vital to identify those with a germline predisposition to develop BIA-ALCL when exposed to a textured implant, and to identify targets for precision anti-BIA-ALCL therapeutics.To determine if there are recurrent gene mutations in BIA-ALCL patients in a cohort at a single institution.Ten patients were included that were diagnosed with BIA-ALCL between April 2015 and May 2020. Whole exome sequencing (WES) was performed on 8 tumor and normal BIA-ALCL samples and whole genome sequencing (WGS) was performed on 3 BIA-ALCL fluid samples. Samples were sequenced on an Illumina NovaSeq 6000. Data was analyzed using the Illumina DRAGEN Bio-IT Platform v3.8 workflow.This study was carried out at Barnes Jewish Hospital/Siteman Cancer Center.Patients were included if they have a pathology proven diagnosis of BIA-ALCL.Incidence and quantification of recurrent mutations in tumor samples of patients with BIA-ALCL evaluated via WES and WGS.Nearly all BIA-ALCLs showed substantial CNAs. Most patients had missense mutations in large genes with predominantly C to T transitions. Two cases had STAT3 mutations, consistent with previously reported data. Whole genome sequencing showed a critically deleted 7Mb region on chromosome 11 at 11q22.3 region in all 3 samples evaluated. This region contains the ATM gene which upon deletion in mouse models has shown an increased number of tumors. Clinically, the overall prognosis of BIA-ALCL was favorable; one patient passed from complications.There are no highly recurrent mutations in BIA-ALCL, however, 11q22.3 deletions were consistent across WGS cases and present in some exomes. Given the small sample size due to the rarity of the disease, genomic evaluation of a larger cohort is necessary to confirm this finding. Financial support for this study was provided by the Aesthetic Surgery Education Research Foundation and Barnes Hospital Foundation.