Back to Search
Start Over
Genomic and Immunologic Characterization of INI1-Deficient Pediatric Cancers.
- Source :
-
Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2020 Jun 15; Vol. 26 (12), pp. 2882-2890. Date of Electronic Publication: 2020 Mar 02. - Publication Year :
- 2020
-
Abstract
- Purpose: Several aggressive pediatric cancers harbor alterations in SMARCB1 , including rhabdoid tumors, epithelioid sarcoma, and chordoma. As tumor profiling has become more routine in clinical care, we investigated the relationship between SMARCB1 genetic variants identified by next-generation sequencing (NGS) and INI1 protein expression. Therapeutic approaches for INI1-deficient tumors are limited. Early reports suggest a potential role for immune checkpoint inhibition in these patients. Thus, we also investigated PD-L1 and CD8 expression in INI1-negative pediatric brain and solid tumors.<br />Experimental Design: We performed immunohistochemistry (IHC) for INI1 and immune markers (PD-L1, CD8, and CD163) and NGS on tumor samples from 43 pediatric patients who had tumors with INI1 loss on previous IHC or SMARCB1 genomic alterations on prior somatic sequencing.<br />Results: SMARCB1 two-copy deletions and inactivating mutations on NGS were associated with loss of INI1 protein expression. Single-copy deletion of SMARCB1 was not predictive of INI1 loss in tumor histologies not known to be INI1-deficient. In the 27 cases with INI1 loss and successful tumor sequencing, 24 (89%) had a SMARCB1 alteration detected. In addition, 47% (14/30) of the patients with INI1-negative tumors had a tumor specimen that was PD-L1 positive and 60% (18/30) had positive or rare CD8 staining. We report on 3 patients with INI1-negative tumors with evidence of disease control on immune checkpoint inhibitors.<br />Conclusions: A significant proportion of the INI1-negative tumors express PD-L1, and PD-L1 positivity was associated with extracranial tumor site. These results suggest that clinical trials of immune checkpoint inhibitors are warranted in INI1-negative pediatric cancers.<br /> (©2020 American Association for Cancer Research.)
- Subjects :
- Adolescent
B7-H1 Antigen antagonists & inhibitors
B7-H1 Antigen genetics
Child
Child, Preschool
Female
Follow-Up Studies
Gene Expression Regulation, Neoplastic
High-Throughput Nucleotide Sequencing
Humans
Infant
Male
Neoplasms drug therapy
Neoplasms genetics
Neoplasms immunology
Prognosis
SMARCB1 Protein genetics
B7-H1 Antigen metabolism
Biomarkers, Tumor genetics
Immune Checkpoint Inhibitors therapeutic use
Mutation
Neoplasms pathology
SMARCB1 Protein deficiency
Subjects
Details
- Language :
- English
- ISSN :
- 1557-3265
- Volume :
- 26
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Clinical cancer research : an official journal of the American Association for Cancer Research
- Publication Type :
- Academic Journal
- Accession number :
- 32122923
- Full Text :
- https://doi.org/10.1158/1078-0432.CCR-19-3089