Whole-exome sequencing identifies a somatic missense mutation of NBN in clear cell sarcoma of the salivary gland.
Clear cell sarcoma (CCS) is a rare, low-grade carcinoma commonly located in the distal extremities of young adults involving tendons and aponeuroses. CCS is characterized by its poor prognosis due to late diagnosis, multiple local recurrence, propensity to late metastases, and a high rate of tumor-related mortality. The genetic cause for CCS is thought to be EWSR1 gene translocation. However, CCS lacking a translocation may have other, as yet uncharacterized, genetic mutations that can cause the same pathological effect. 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. In conclusion, we here report a somatic missense mutation c.1061C>T (p.P354L) in the NBN gene in a patient with CCS lacking an EWSR1-ATF1 fusion. Our findings broaden the genotypic spectrum of CCS and provide new molecular insight that should prove useful in the future clinical genetic diagnosis of CCS.
Department of Stomatology, Chinese PLA General Hospital, Beijing 100853, P.R. China.
Lei
L
Zhang
Department of Stomatology, Beijing Aviation General Hospital, Beijing 100012, P.R. China.
Zhen
Z
Jia
Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, P.R. China.
Fengbiao
F
Mao
Department of Stomatology, Chinese PLA General Hospital, Beijing 100853, P.R. China.
Yueyi
Y
Shi
Department of Stomatology, Chinese PLA General Hospital, Beijing 100853, P.R. China.
Rong Fa
RF
Bu
Department of Stomatology, Beijing Aviation General Hospital, Beijing 100012, P.R. China.
Baorong
B
Zhang
D000328:Adult; D018797:Cell Cycle Proteins / Q000235:genetics*; D019295:Computational Biology; D059472:Exome; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D009687:Nuclear Proteins / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D012468:Salivary Gland Neoplasms / Q000235:genetics*; D018227:Sarcoma, Clear Cell / Q000235:genetics*
D018797:Cell Cycle Proteins; C560860:EWSR1-ATF1 fusion protein, human; C112156:NBN protein, human; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion