The JAK-STAT pathway as well as epigenetics may play a role in the development of breast implant–associated anaplastic large-cell lymphoma (BIA-ALCL), according to the genomic characteristics of a small group of BIA-ALCL cases recently published in Blood.
Evidence increasingly suggests that women who receive textured breast implants are at an increased risk for developing BI-ALCL, Cancer Therapy Advisor previously reported.
Whole-exome sequencing was performed on 22 samples from BIA-ALCL cases, which was made up of 10 tumor and 12 in situ subtypes, and the sequencing results were compared with matched germline DNA samples.
The sequencing revealed 16 of 22 samples (64%) had alterations in JAK-STAT pathway, and the most commonly mutated genes were STAT3 (41%) and JAK1 (18%). Additional genes that were mutated were SOCS3 (9%), SOCS1 (5%), PTPN1 (5%), and STAT5B (5%).
Mutations in epigenetic regulators and histone modifiers were also found, with mutations of genes coding for H3K4 methyltransferases being most common, followed by mutations of genes coding for chromodomain helicase DNA-binding proteins.
To confirm the whole-exome sequencing findings, targeted deep sequencing was performed on 12 cases previously tested and 12 new cases. The previously tested cases had a “perfect concordance” with the targeted deep-sequencing results, and 50% of the newly added cases had at least 1 mutation in the JAK-STAT pathway.
In all, of the 34 total samples analyzed using whole-exome or targeted deep sequencing, 74% had mutations in epigenetic regulators and histone modifiers and 59% had mutations in the JAK-STAT pathway.
The study authors concluded that “this genomic characterization” of the BIA-ALCL cases “not only confirms the key role of the JAK-STAT pathway but also highlights the importance of epigenetics in [BIA-ALCL] pathogenesis.”
“Compounds targeting these molecular alterations,” they wrote, “might be considered in the future to treat the small proportion of [BIA-ALCL] patients with aggressive refractory disease.”
Laurent C, Nicolae A, Laurent C, et al. Gene alterations in epigenetic modifiers and JAK-STAT signaling are frequent in breast implant-associated ALCL. Blood. 2020;135(5):360-370.