title: PMS2 gene mutation results in DNA mismatch repair system failure in a case of adult granulosa cell tumor.
abstract: BACKGROUND
  Granulosa cell tumors are rare ovarian malignancies. Their characteristics include unpredictable indolent growth with malignant potential and late recurrence. Approximately 95% are of adult type. Recent molecular studies have characterized the FOXL2 402C > G mutation in adult granulosa cell tumor. Our previous case report showed that unique FOXL2 402C > G mutation and defective DNA mismatch repair system are associated with the development of adult granulosa cell tumor.
  
  
  RESULTS
  In this study, the DNA sequences of four genes, MSH2, MLH1, MSH6, and PMS2, in the DNA mismatch repair system were determined via direct sequencing to elucidate the exact mechanism for the development of this granulosa cell tumor. The results showed that two missense germline mutations, T485K and N775L, inactivate the PMS2 gene.
  
  
  CONCLUSIONS
  The results of this case study indicated that although FOXL2 402C > G mutation determines the development of granulosa cell tumor, PMS2 mutation may be the initial driver of carcinogenesis. Immunohistochemistry-based tumor testing for mismatch repair gene expression may be necessary for granulosa cell tumors to determine their malignant potential or if they are part of Lynch syndrome.
authors.affiliation: Department of Obstetrics and Gynecology, Jen-Ai Hospital, Taichung, Taiwan.
authors.forename: Wen-Chung
authors.initials: WC
authors.lastname: Wang
authors.affiliation: Department of Medical Laboratory and Biotechnology, Chung Shan Medical University, No.110, Sec. 1, Chien Kuo N. Road, Taichung, 402, Taiwan, Republic of China.
authors.forename: Ya-Ting
authors.initials: YT
authors.lastname: Lee
authors.affiliation: Department of Medical Laboratory and Biotechnology, Chung Shan Medical University, No.110, Sec. 1, Chien Kuo N. Road, Taichung, 402, Taiwan, Republic of China. yenchein@csmu.edu.tw.
authors.forename: Yen-Chein
authors.initials: YC
authors.lastname: Lai
mesh_terms: D000328:Adult; D000483:Alleles; D014408:Biomarkers, Tumor; D053843:DNA Mismatch Repair; D005091:Exons; D005260:Female; D000074842:Forkhead Box Protein L2; D051858:Forkhead Transcription Factors / Q000235:genetics; D005838:Genotype; D006106:Granulosa Cell Tumor / Q000235:genetics*; D006801:Humans; D007438:Introns; D000070976:Mismatch Repair Endonuclease PMS2 / Q000235:genetics*; D009154:Mutation; D017422:Sequence Analysis, DNA
chemical_list: D014408:Biomarkers, Tumor; C421604:FOXL2 protein, human; D000074842:Forkhead Box Protein L2; D051858:Forkhead Transcription Factors; C094934:PMS2 protein, human; D000070976:Mismatch Repair Endonuclease PMS2
keywords: DNA mismatch repair system; Direct sequencing; Granulosa cell tumor