We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Characteristics of glioblastomas and immune microenvironment in a Chinese family with Lynch syndrome and concurrent porokeratosis.
- Authors
Zhi-Gang Yao; Fang Hua; Zuo-Hua Yin; Ying-Jie Xue; Yang-Hao Hou; Yi-Cong Nie; Zhi-Ming Zheng; Miao-Qing Zhao; Xiao-Hong Guo; Chao Ma; Xiao-Kang Li; Zhou Wang; Guang-Cun Liu; Gui-Hui Zhang
- Abstract
Background: Lynch syndrome (LS)-associated glioblastoma (GBM) is rare in clinical practice, and simultaneous occurrence with cutaneous porokeratosis is even rarer. In this study, we analyzed the clinicopathological and genetic characteristics of LS-associated GBMs and concurrent porokeratosis, as well as evaluated the tumor immune microenvironment (TIME) of LS-associated GBMs. Methods: Immunohistochemical staining was used to confirm the histopathological diagnosis, assess MMR and PD-1/PD-L1 status, and identify immune cell subsets. FISH was used to detect amplification of EGFR and PDGFRA, and deletion of 1p/19q and CDKN2A. Targeted NGS assay analyzed somatic variants, MSI, and TMB status, while whole-exome sequencing and Sanger sequencing were carried out to analyze the germline mutations. Results: In the LS family, three members (I:1, II:1 and II:4) were affected by GBM. GBMs with loss of MSH2 and MSH6 expression displayed giant and multinucleated bizarre cells, along with mutations in ARID1A, TP53, ATM, and NF1 genes. All GBMs had TMB-H but notMSI-H. CD8+ T cells and CD163+macrophageswere abundant in each GBM tissue. The primary and recurrent GBMs of II:1 showed mesenchymal characteristics with high PD-L1 expression. The family members harbored a novel heterozygous germline mutation in MSH2 and FDPS genes, confirming the diagnosis of LS and disseminated superficial actinic porokeratosis. Conclusion: LS-associated GBM exhibits heterogeneity in clinicopathologic and molecular genetic features, as well as a suppressive TIME. The presence of MMR deficiency and TMB-H may serve as predictive factors for the response to immune checkpoint inhibitor therapy in GBMs. The identification of LSassociated GBM can provide significant benefits to both patients and their family members, including accurate diagnosis, genetic counseling, and appropriate screening or surveillance protocols. Our study serves as a reminder to clinicians and pathologists to consider the possibility of concurrent genetic syndromes in individuals or families.
- Subjects
HEREDITARY nonpolyposis colorectal cancer; MULTINUCLEATED giant cells; GLIOBLASTOMA multiforme; IMMUNOSTAINING; IMMUNE checkpoint inhibitors; GENETIC counseling
- Publication
Frontiers in Oncology, 2023, p1
- ISSN
2234-943X
- Publication type
Article
- DOI
10.3389/fonc.2023.1194232