title: Oncogenic alterations in papillary thyroid cancers of young patients.
abstract: BACKGROUND
  Papillary thyroid carcinoma (PTC) in young people usually has an aggressive initial presentation, though a good general prognosis despite recurrences in 10%-20% of patients. A number of genetic alterations that activate the mitogen-activated protein kinase (MAPK) pathway have been found in PTC. Some of these alterations have been identified as prognostic factors of PTC in adults. The objective of the current study was to comprehensively characterize all known oncogenic alterations of the MAPK pathway in young people.
  
  
  METHODS
  One hundred three PTCs removed from 9 children, 19 adolescents, and 75 young adults were submitted to molecular analyses.
  
  
  RESULTS
  Altogether, 57 alterations were found in 56 PTCs (55%) corresponding to V600E BRAF in 20.3%, RAS mutations in 12.6%, RET/PTC 1 in 11.6%, RET/PTC 3 in 8.7%, and rearrangement of NTRK in 1.9%. The prevalence of all alterations increased with age (22.2% in children; 52.6% in adolescents, 51.4% in adults 20-25 years, and 55.1% in adults 25-35 years). Prevalence increased from 39.2% earlier to 61.3% after 20 years mainly due to BRAF mutations. Classic-type PTC was associated with a larger prevalence of alterations, predominantly BRAF and RET/PTC, whereas the follicular variant was chiefly associated with RAS. RET/PTC (1 and 3) was significantly associated with extrathyroid extension (ET) and lymph node metastasis (es) (LNM). This association was found in the adult group. There were no associations of BRAF or RAS mutations with ET or LNM. A 3-year median follow up was available for 90 patients. RET/PTC 1 and 3 was associated with short-term disease dissemination (cervical lymph node recurrences and distant metastases) in young adults (p=0.001). Persistent illness was more prevalent in patients with (15%) than in patients without (7%) genetic alterations.
  
  
  CONCLUSIONS
  PTCs in young patients display a low prevalence of the already identified oncogenic alterations. The increasing prevalence with age is mainly due to V600E BRAF mutation. There is no relation between tumor aggressiveness and BRAF mutation. There is a relation between the presence of RET/PTC (1 and 3) and the histological and clinical short-term aggressiveness of PTC in the population of young adults. Such a relation is not found in children and adolescents.
authors.affiliation: Centre de Recherche en Cancérologie de Lyon, Rhône-Alpes Registry of Thyroid Cancers, Université Lyon UMR INSERM U1052, CNRS 5286, Lyon-R.T.H. Laennec School of Medicine, Lyon, France. genevieve.sassolas@chu-lyon.fr
authors.forename: Geneviève
authors.initials: G
authors.lastname: Sassolas
authors.forename: Zakia
authors.initials: Z
authors.lastname: Hafdi-Nejjari
authors.forename: Angelo
authors.initials: A
authors.lastname: Ferraro
authors.forename: Myriam
authors.initials: M
authors.lastname: Decaussin-Petrucci
authors.forename: Bernard
authors.initials: B
authors.lastname: Rousset
authors.forename: Françoise
authors.initials: F
authors.lastname: Borson-Chazot
authors.forename: Eleonora
authors.initials: E
authors.lastname: Borbone
authors.forename: Nicole
authors.initials: N
authors.lastname: Berger
authors.forename: Alfredo
authors.initials: A
authors.lastname: Fusco
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D002277:Carcinoma; D002291:Carcinoma, Papillary / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D002648:Child; D005260:Female; D011905:Genes, ras; D006801:Humans; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics*; D009154:Mutation; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D011379:Prognosis; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D055815:Young Adult
chemical_list: D015514:Oncogene Proteins, Fusion; D011505:Protein-Tyrosine Kinases; C093573:ret-PTC fusion oncoproteins, human; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D020928:Mitogen-Activated Protein Kinases