title: Low prevalence of the somatic M918T RET mutation in micro-medullary thyroid cancer.
abstract: BACKGROUND
  The prevalence of RET somatic mutations in sporadic medullary thyroid cancer (MTCs) is ∼40%-50%, and the most frequent somatic mutation is M918T. RET-positive MTCs have been demonstrated to have a more advanced stage at diagnosis and a worse outcome.
  
  
  OBJECTIVE
  The aim of the present work was to compare the prevalence of RET somatic mutations in sporadic microMTCs (<1 cm) and in larger MTCs.
  
  
  METHODS
  We analyzed the M918T RET point mutation in 160 sporadic MTC cases. Tumors were classified according to their size: group A, <1 cm; group B, >1 and <2 cm; group C, >2 and <3 cm; and group D, >3 cm.
  
  
  RESULTS
  The overall prevalence of the somatic M918T RET mutation was 19.4% (31/160). RET mutations were distributed differently among the four groups. The prevalence was 11.3% (6/53) in group A, 11.8% (8/68) in group B, 31.8% (7/22) in group C, and 58.8% (10/17) in group D, exhibiting an increase with increasing size of the tumor. When comparing the prevalence of mutations in the four groups, we found a lower prevalence in microMTCs (p<0.0001).
  
  
  CONCLUSIONS
  The overall prevalence of RET somatic mutations was lower than expected, and the prevalence of the somatic M918T RET mutation was significantly lower in microMTCs than in larger tumors. To explain this finding, we can hypothesize either that other oncogene(s) might be responsible for the majority of microMTC, thus identifying a tumor subset, or that the RET mutation might, or might not, occur later during tumor progression.
authors.affiliation: Department of Endocrinology and Metabolism, University of Pisa, Via Paradisa 2, Pisa, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Romei
authors.forename: Clara
authors.initials: C
authors.lastname: Ugolini
authors.forename: Barbara
authors.initials: B
authors.lastname: Cosci
authors.forename: Liborio
authors.initials: L
authors.lastname: Torregrossa
authors.forename: Agnese
authors.initials: A
authors.lastname: Vivaldi
authors.forename: Raffaele
authors.initials: R
authors.lastname: Ciampi
authors.forename: Alessia
authors.initials: A
authors.lastname: Tacito
authors.forename: Fulvio
authors.initials: F
authors.lastname: Basolo
authors.forename: Gabriele
authors.initials: G
authors.lastname: Materazzi
authors.forename: Paolo
authors.initials: P
authors.lastname: Miccoli
authors.forename: Paolo
authors.initials: P
authors.lastname: Vitti
authors.forename: Aldo
authors.initials: A
authors.lastname: Pinchera
authors.forename: Rossella
authors.initials: R
authors.lastname: Elisei
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018278:Carcinoma, Neuroendocrine; D045744:Cell Line, Tumor; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005260:Female; D006367:HeLa Cells; D006801:Humans; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D015995:Prevalence; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: D051096:Proto-Oncogene Proteins c-ret