JAK2, PD-L1, and PD-L2 (9p24.1) amplification in metastatic mucosal and cutaneous melanomas with durable response to immunotherapy

Hum Pathol. 2019 Jun:88:87-91. doi: 10.1016/j.humpath.2018.08.032. Epub 2018 Sep 18.

Abstract

As immune checkpoint inhibitors are rapidly developing into the standard of care for patients with advanced melanoma, the value of diagnostic metrics to predict response to immunotherapy is steadily increasing. Next-generation sequencing-based parameters include tumor mutation burden (TMB) and genomic amplification of PD-L1/PD-L2/JAK2 at 9p24.1. At present, there are limited studies documenting response to checkpoint blockade in 9p24.1-amplified solid tumors. Herein, we have compared a cutaneous melanoma with a mucosal melanoma, both with 9p24.1 amplifications and durable response to immunotherapy. Although the cutaneous melanoma had a high TMB, the mucosal melanoma had a lower TMB compared with the mean TMB for all melanomas within the institutional clinical sequencing cohort. In summary, PD-L1/PD-L2/JAK2 amplification was associated with durable response to therapy for both cases, and this genomic signature is a potential valuable metric in predicting response to immunotherapy.

Keywords: 9p24.1 amplification; Immunotherapy; JAK2; Melanoma; PD-L1; PD-L2.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • B7-H1 Antigen / genetics*
  • Female
  • Gene Amplification*
  • Humans
  • Immunotherapy*
  • Janus Kinase 2 / genetics*
  • Male
  • Melanoma / genetics*
  • Melanoma / pathology
  • Melanoma / therapy
  • Mucous Membrane / pathology
  • Neoplasm Metastasis / genetics
  • Neoplasm Metastasis / pathology
  • Neoplasm Metastasis / therapy
  • Programmed Cell Death 1 Ligand 2 Protein / genetics*
  • Skin Neoplasms / genetics
  • Skin Neoplasms / pathology
  • Skin Neoplasms / therapy
  • Treatment Outcome

Substances

  • B7-H1 Antigen
  • CD274 protein, human
  • PDCD1LG2 protein, human
  • Programmed Cell Death 1 Ligand 2 Protein
  • JAK2 protein, human
  • Janus Kinase 2