title: Novel tandem germline RET proto-oncogene mutations in a patient with multiple endocrine neoplasia type 2B: report of a case and a literature review of tandem RET mutations with in silico analysis.
abstract: BACKGROUND
  Multiple endocrine neoplasia type 2B (MEN2B) is the rarest and most aggressive form of MEN2. MEN2B cases usually carry either an M918T or A883T mutation of the RET, but to date, there are 3 atypical MEN2B caused by tandem mutations.
  
  
  RESULTS
  A 32-year-old woman with no family history of medullary thyroid carcinoma (MTC) presented with a neck tumor and multiple mucosal nodules. She was diagnosed with MEN2B. Genetic analyses of RET revealed that she had 2 mutations, Q781R and V804M. Subclone and genetic analyses revealed that Q781R was on the paternal allele and V804M was a de novo. In silico analysis of the tandem mutations showed a high prediction score.
  
  
  CONCLUSIONS
  We describe a novel combination of tandem RET mutations (Q781R/V804M) in a MEN2B-like patient. In silico analysis showed a high prediction score, which was compatible with the clinical phenotype in the present case.
authors.affiliation: Department of Endocrinology and Metabolism, National Hospital Organization, Kyoto Medical Center, Kyoto, Japan.
authors.forename: Kanako-Tanase
authors.initials: KT
authors.lastname: Nakao
authors.forename: Takeshi
authors.initials: T
authors.lastname: Usui
authors.forename: Mayumi
authors.initials: M
authors.lastname: Ikeda
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Mori
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Sachiko-Tsukamoto
authors.initials: ST
authors.lastname: Kawashima
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Nanba
authors.forename: Akiko
authors.initials: A
authors.lastname: Yuno
authors.forename: Tamiko
authors.initials: T
authors.lastname: Tamanaha
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Tagami
authors.forename: Mitsuhide
authors.initials: M
authors.lastname: Naruse
authors.forename: Ryo
authors.initials: R
authors.lastname: Asato
authors.forename: Akira
authors.initials: A
authors.lastname: Shimatsu
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution; D002116:Calcitonin / Q000097:blood; D003198:Computer Simulation; D005260:Female; D005838:Genotype; D018095:Germ-Line Mutation; D006801:Humans; D008207:Lymphatic Metastasis; D009061:Mouth Mucosa / Q000473:pathology; D018814:Multiple Endocrine Neoplasia Type 2b / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D037981:Neck Dissection; D010375:Pedigree; D016133:Polymerase Chain Reaction; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D013965:Thyroidectomy
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D002116:Calcitonin; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human
keywords: MEN2B; RET; de novo; in silico; tandem mutation