Whole exome sequencing identi fies a somatic missense mutation of Nibrin gene in clear cell sarcoma of the salivary gland

Objective To investigate the genetic variation in the clear cell sarcoma (CCS) of the salivary gland and to broaden the genotypic spectrum of CCS. Methods Whole exome sequencing analysis was performed on DNA of venous blood and cancer tissue of an male CCS patient to scan the candidate mutations.Sanger sequencing was used to verify these candidate mutations in the tumor tissue, matched blood sample and peritumor tissue (adjacent non-tumorous tissue).Clinical and pathological examinations were also performed. Results A combination of whole exome sequencing and Sanger sequencing of cancer tissue and venous blood from a patient diagnosed with CCS of the salivary gland revealed a somatic missense mutation, c.1061C＞ T (p.P354L), in exon 9 of the Nibrin gene (NBN).This somatic missense mutation led to the conversion of proline to leucine (p.P354L), resulting in deleterious effects for the NBN protein.Multiple-sequence alignments showed that codon 354, where the mutation (c.1061C＞ T) occurs, is located within a phylogenetically conserved region. Conclusion We report a somatic missense mutation c.1061C＞ T (p.P354L) in NBN gene for a Chinese patient with CCS without EWSR1-ATF1 fusion.Our findings broaden the genotypic spectrum of CCS and provide new molecular insight into future clinical genetic diagnosis for CCS.