Whole-exome sequencing shows no specific mutation in ovarian teratoma of NMDAR-antibody encephalitis
Yoonhyuk Jang1, Soo Hyun Ahn1, Gwanghoon Lee1, Kyung-Il Park2, Sang Kun Lee3, Kon Chu1, Cheol Lee1, Jae Kyung Won1, Soon-Tae Lee4
1Seoul National University Hospital, 2Seoul National University Hospital Gangnam center, 3Seoul national University Hospital, 4Department of Neurology, Seoul National University Hospital
Objective:
To investigate mutations specific to the N-methyl-D-aspartate receptor (NMDAR)-associated teratoma to reveal the autoimmunity mechanism
Background:
N-methyl-D-aspartate receptor (NMDAR)-antibody encephalitis is the most common form of autoimmune encephalitis, about 40% of which is caused by ovarian teratoma. However, it is unknown why only a small population of ovarian teratoma causes the autoimmunity while the majority of the teratoma don’t. This study aimed to investigate any driver mutations specific to the NMDAR-associated teratoma to reveal the autoimmunity mechanism.
Design/Methods:
We included 17 ovarian teratomas derived from 15 patients with NMDAR-antibody encephalitis and 18 control ovarian teratoma from 30 patients without encephalitis. All the samples were genotyped by the SureSelect V6-Post Exome Capture kit (Agilent, CA, USA). The exome data were analyzed with R version 4.06 (Vienna, Austria) and the MUTALISK program (National cancer center, Goyang-si, Korea).
Results:
The two groups with and without NMDAR-antibody encephalitis had a mean age of 23.9 and 24.4 years, respectively. The average teratoma size was smaller in the group with encephalitis (3.0±2.1 cm vs 10.9±2.1, respectively). With the criteria lower than 1% of allele frequency with 1000 genome phase 3 (1000Gp3) and the Exome Aggregation Consortium (ExAC), 34 exomes were passed in our samples. Of these, no exome showed significantly different mutations between the groups of teratoma with and without NMDAR-antibody encephalitis. From the MUTALISK analysis, there was no significant difference in the mutation pattern signature in exomes between the two groups.
Conclusions:
This study shows that there is no difference in the mutation profile in protein-coding genes between the ovarian teratoma causing NMDAR-antibody encephalitis and the control teratoma. This result implies that post-transcriptional immune pathogeneses are involved in the autoimmune recognition of ovarian teratoma with NMDAR-antibody encephalitis.