Work

Neurofibromatosis-1 Gene Mutational Profiles Differ Between Syndromic Disease and Sporadic Cancers

Year: 2022

Type: article

Abstract: Objectives Variants in the neurofibromatosis type 1 (NF1) gene are not only responsible for the NF1 cancer predisposition syndrome, but also frequently identified in cancers arising in the general population. While germline variants are pathogenic, it is not known whether those that arise in cancer (somatic variants) are passenger or driver variants. To address this question, we sought to define the landscape of NF1 variants in sporadic cancers. Methods NF1 variants in sporadic cancers were compiled using data curated on the c-Bio database and compared with published germline variants and Genome Aggregation Database data. Pathogenicity was determined using Polyphen and Sorting Intolerant From Tolerant prediction tools. Results The spectrum of NF1 variants in sporadic tumors differ from those most commonly seen in individuals with NF1. In addition, the type and location of the variants in sporadic cancer differ from germline variants, where a high proportion of missense variants were found. Finally, many of the sporadic cancer NF1 variants were not predicted to be pathogenic. Discussion Taken together, these findings suggest that a significant proportion of NF1 variants in sporadic cancer may be passenger variants or hypomorphic alleles. Further mechanistic studies are warranted to define their unique roles in nonsyndromic cancer pathobiology.

Source: Neurology Genetics

DOI: 10.1212/nxg.0000000000200003

Authors: Alice F. Bewley, Titilope M. Akinwe, Tychele N. Turner, David H. Gutmann

Institution: Washington University in St. Louis

Language: English

Topic: Neurofibromatosis and Schwannoma Cases

Subfield: Neurology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,300