# 9p24.1 alteration of the PD-1 ligand loci

Source: https://onco.cc/biomarkers/pd-ligand-9p24-alteration/  
OnCo record `pd-ligand-9p24-alteration` (Biomarker). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

An extra stretch of chromosome 9 that carries both of the molecules a tumour uses to switch off T cells, plus the enzyme that turns them up further. Nearly every classical Hodgkin lymphoma has it, which is why checkpoint drugs work so well there and so poorly in most other lymphomas.

## Summary

The 9p24.1 amplicon contains CD274 and PDCD1LG2, the genes for the two PD-1 ligands, and JAK2. Amplifying it raises the ligands twice over, by gene dose and by JAK2-driven transcription, and JAK2 amplification also increases sensitivity to JAK2 inhibition in the laboratory. The alteration is disease-specific: it is restricted to nodular sclerosing Hodgkin lymphoma, the subtype most closely related to mediastinal large B-cell lymphoma, and to mediastinal large B-cell lymphoma itself (Green 2010).

In 108 newly diagnosed classical Hodgkin lymphomas evaluated by fluorescence in situ hybridisation, 97% had concordant alterations of both loci: polysomy in 5 of 108, copy gain in 61 of 108 and amplification in 39 of 108, and higher-level gain predicted shorter progression-free survival (Roemer 2016). Alongside it, recurrent CIITA fusions, found in 38% of primary mediastinal B-cell lymphomas and 15% of classical Hodgkin lymphomas across 263 B-cell lymphomas, lower MHC class II on the tumour cell and place the ligands under new promoters (Steidl 2011).

This is the clearest genetic explanation in oncology for why one disease answers checkpoint blockade: PD-1 blockade gave an objective response in 20 of 23 heavily pre-treated Hodgkin patients, 87%, most of whom had already failed both autologous transplant and brentuximab vedotin (Ansell 2015). What predicts complete remission within that group is not MHC class I but MHC class II expression on the Hodgkin and Reed-Sternberg cells, which suggests the effector is a CD4 T cell (Roemer 2018).

## Fields

- Kind: Biomarker
- Last checked: 2026-09-30
- Also known as: 9p24.1 amplification; CD274 amplification; PDCD1LG2 amplification; PD-1 ligand copy gain; 9p24.1 copy gain
- Tags: biomarker; lymphoma

## Sources

- Green et al., Blood 2010: selective 9p24.1 amplification and PD-1 ligand induction through JAK2 in Hodgkin lymphoma and mediastinal large B-cell lymphoma: https://doi.org/10.1182/blood-2010-05-282780
- Roemer et al., J Clin Oncol 2016: PD-L1 and PD-L2 genetic alterations in 108 classical Hodgkin lymphomas: https://doi.org/10.1200/JCO.2016.66.4482
- Roemer et al., J Clin Oncol 2018: MHC class II and PD-L1 expression predict outcome after PD-1 blockade in classical Hodgkin lymphoma (CheckMate 205): https://doi.org/10.1200/JCO.2017.77.3994
- Ansell et al., N Engl J Med 2015: nivolumab in relapsed or refractory Hodgkin lymphoma (23 patients): https://doi.org/10.1056/NEJMoa1411087

## Connected records

- cancers: [Hodgkin lymphoma](https://onco.cc/cancers/hodgkin-lymphoma/), [Non-Hodgkin lymphoma (all types)](https://onco.cc/cancers/non-hodgkin-lymphoma/), [Primary mediastinal (thymic) large B-cell lymphoma](https://onco.cc/cancers/primary-mediastinal-b-cell-lymphoma/)
- technologies: [Cytogenetics and FISH](https://onco.cc/technologies/cytogenetics-fish/), [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/)
- targets: [CIITA](https://onco.cc/targets/ciita/), [JAK2](https://onco.cc/targets/jak2/)
- drugs: [Nivolumab](https://onco.cc/drugs/nivolumab/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/)
- pathways: [Antigen presentation & immune editing](https://onco.cc/pathways/antigen-presentation-immunoediting/), [JAK-STAT signalling](https://onco.cc/pathways/jak-stat/), [PD-1 / PD-L1 immune checkpoint & T-cell activation](https://onco.cc/pathways/pd1-checkpoint/)
- terms: [FISH / ISH (in situ hybridisation)](https://onco.cc/terms/fish/), [Gene amplification and copy-number change](https://onco.cc/terms/gene-amplification/), [The Hodgkin microenvironment: when the cancer cell is the minority](https://onco.cc/terms/lymphoma-bio-hodgkin-microenvironment/)

---
JSON: https://onco.cc/api/v1/entities/pd-ligand-9p24-alteration.json