title: CDKN1B V109G polymorphism a new prognostic factor in sporadic medullary thyroid carcinoma.
abstract: BACKGROUND
  CDKN1B encodes the cyclin-dependent kinase inhibitor p27Kip1 and is mutated in multiple endocrine neoplasia-like syndromes. CDKN1B also harbors single nucleotide polymorphisms; the T/G transversion at nucleotide 326 (the V109G variant) has been reported to be protective in breast, hereditary prostate, and pancreatic tumors. Association of CDNK1B mutations or polymorphisms with sporadic medullary thyroid carcinoma (MTC) has not been investigated yet.
  
  
  OBJECTIVE
  We screened germline DNA from 84 patients affected by sporadic MTC and 90 healthy age- and gender-matched controls for CDKN1B mutations or polymorphisms by PCR amplification and sequencing of the amplicons. We also tested all germline and 50 tumor tissue DNA for RET proto-oncogene mutations. Computed tomography, ultrasound scans, and serum calcitonin were carried out before surgery and during the follow-up and associated with CDKN1B polymorphism and disease remission.
  
  
  RESULTS
  The T/G transversion at nucleotide 326 was the only DNA variation detected. The overall frequency of the T/G and G/G alleles in combination was 46.4%. This variant (V109G) was correlated with post-operative calcitonin levels in the normal range and biochemical remission. Conversely, the wild-type (T/T) allele was associated with post-operative calcitonin levels above normal and a higher risk to develop clinical recurrence and distant metastases. Somatic RET mutations were significantly associated with a more aggressive behavior especially in wild-type allele-bearing patients.
  
  
  CONCLUSIONS
  Collectively, in sporadic MTC, the CDKN1B V109G polymorphism correlates with a more favorable disease progression than the wild-type allele and might be considered a new promising prognostic marker.
authors.affiliation: Dipartimento Medico-Chirurgico di Internistica Clinica e Sperimentale F. Magrassi e A. Lanzara, Seconda Università di Napoli, 80131 Napoli, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Pasquali
authors.forename: Luisa
authors.initials: L
authors.lastname: Circelli
authors.forename: Antongiulio
authors.initials: A
authors.lastname: Faggiano
authors.forename: Massimo
authors.initials: M
authors.lastname: Pancione
authors.forename: Andrea
authors.initials: A
authors.lastname: Renzullo
authors.forename: Rossella
authors.initials: R
authors.lastname: Elisei
authors.forename: Cristina
authors.initials: C
authors.lastname: Romei
authors.forename: Giacomo
authors.initials: G
authors.lastname: Accardo
authors.forename: Viviana Raffaella
authors.initials: VR
authors.lastname: Coppola
authors.forename: Maurizio
authors.initials: M
authors.lastname: De Palma
authors.forename: Piero
authors.initials: P
authors.lastname: Ferolla
authors.forename: Franco
authors.initials: F
authors.lastname: Grimaldi
authors.forename: Annamaria
authors.initials: A
authors.lastname: Colao
authors.forename: Vittorio
authors.initials: V
authors.lastname: Colantuoni
mesh_terms: D000328:Adult; D002116:Calcitonin / Q000097:blood; D018278:Carcinoma, Neuroendocrine; D050760:Cyclin-Dependent Kinase Inhibitor p27; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D016016:Proportional Hazards Models; D000090063:Proto-Oncogene Mas; D013964:Thyroid Neoplasms / Q000097:blood / Q000235:genetics
chemical_list: C436291:CDKN1B protein, human; D047908:Intracellular Signaling Peptides and Proteins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D050760:Cyclin-Dependent Kinase Inhibitor p27; D002116:Calcitonin