The landscape of chromosome 11q13 amplification in Chinese solid tumor patients and hyperprogressive disease (HPD) clinical example.

Abstract

e15222 Background: Multiple biomarkers are thought to be effective guides in selecting immune checkpoint inhibitors, such as Tumor mutational burden (TMB), PD-L1 and MSI/dMMR. Immunotherapy may be miraculous effective in some patients but many other patients experienced poor prognosis and even tumor overgrowth after immunotherapy in real practice. Previous studies have reported that 11q13 (CCND1, FGF3, FGF4, and FGF19) amplifications were associated with HPD. However, the characterization of chromosome 11q13 amplification in Chinese solid tumor patients are not clear. Methods: A total of 10167 Chinese solid tumor patients’ FFPE and matching blood samples sequenced by next-generation sequencing (NGS) targeting 450 cancer genes were included in this study. Genomic alterations including single nucleotide variants (SNV), insertions and deletions, copy number variations and fusions were assessed. The testing was carried out by a College of American Pathologists (CAP) accredited and Clinical Laboratory Improvement Amendments (CLIA) certified laboratory. Results: Chromosome 11q13 amplifications were identified in 679 (6.7%) Chinese solid tumor patients. The top six tumor types with 11q13 amplification were esophageal carcinoma 43.8%, melanoma 17%, urothelial carcinoma 16%, breast carcinoma 13.4%, head and neck carcinoma 13.1% and hepatocellular carcinoma 9.4%. In 2257 patients with TMB-H (10muts/Mb) / PD-L1 expression / MSI samples, chromosome 11q13 copy number gain were identified in 184 (8.2%) patients. Chromosome 11q13 amplification and MSI were independent events and didn't occur simultaneously. In TMB-H patients, the detection rate of 11q13 amplification was 8.5%, while in PD-L1 positive patients, the amplification rate of 11q13 was 7.4%. In patients with TMB-H and PD-L1 positive, the detection rate of 11q13 amplification was 9.4%. In our clinical practice, we saw example of HPD exist in a lung squamous cell carcinoma patient who was treated with multiple lines of therapy and then used the Nivolumab. The patient underwent genetic testing and was found to be chromosome 11q13 amplified. Conclusions: The proportion of 11q13 amplification was different in different types of solid tumor. Esophageal carcinoma, melanoma and urothelial carcinoma were top three types of solid tumors with 11q13 amplification. The 11q13 amplification did not coincide with MSI but it overlapped with PD-L1 expression or TMB-H. Together, these results may provide immunotherapy guidance in clinical practice.