Work

Human leucocyte antigen class I and II alleles are associated with tumor susceptibility in neurofibromatosis type 1

Year: 2026

Type: article

Abstract: Introduction: mutation. With few exceptions, the identification of specific genotype-phenotype correlations has remained elusive. Methods: We utilized RNA-sequencing, whole exome sequencing data and direct DNA sequencing to determine HLA genotypes for individuals with NF1-associated high-grade glioma (HGG, n=38), low-grade glioma (LGG, n=91), and malignant peripheral nerve sheath tumors (MPNST, n=105). Odds ratios (OR), binomial p-values and false discovery values were calculated by comparing observed carrier frequencies against expected frequencies derived from ethnicity-matched population data. Results: We find that specific HLA class I and II alleles are associated with different NF1 tumor types. For example, HLA-B*40:02 is significantly associated with NF1-MPNST (OR=3.71, p=0.001, Q=0.023), increasing the lifetime risks for MPNST from 10-15.8% to about 36.6% (CI 16.1-57.2%). Discussion: The relative cancer risk for an individual in the general population carrying a risk allele can be high, however, that individual's absolute risk for cancer typically remains very low. In contrast, individuals that carry a risk allele and are also burdened with a tumor predisposition syndrome will have a substantially higher absolute risk to develop a tumor, simply because they start at a higher baseline susceptibility for tumors. The identification of HLA-risk alleles for NF1 tumor development has the potential to improve clinical care and outcomes by prompting risk-adapted screening and treatment. It is important to note that the associations found in this study require validation in an independent prospective cohort.

Source: Frontiers in Immunology

DOI: 10.3389/fimmu.2026.1966259